Multifraction Research Articles

Dose-Effect Relationship of Kidney Function After SABR for Primary Renal Cell Carcinoma: TROG 15.03 FASTRACK II

BackgroundStereotactic ablative body radiotherapy (SABR) is a novel option to treat primary renal cell carcinoma (RCC). However, a high radiation dose may be received by the treated kidney, which may affect its function post-treatment. This study investigates the dose-effect relationship of kidney SABR with posttreatment renal function. MethodsThis was a prespecified secondary endpoint of the multicenter FASTRACK II clinical trial (NCT02613819). Patients received either 26 Gy in a single fraction (SF) for tumors with a maximal diameter of 4 cm or less, or 42 Gy in three fractions (multi-fraction (MF)) for larger tumors. To determine renal function change, 99mTc-DMSA SPECT/CT scans were acquired, and the glomerular filtration rate (GFR) was estimated at baseline, 12-, and 24-months post-treatment. Imaging datasets were rigidly registered to the planning CT where kidneys were segmented to calculate dose-response curves. ResultsFrom 71 enrolled patients, data from 36 (51%) and 26 (37%) patients were included in this study based on availability of post-treatment data at 12- and 24-months, respectively. The ipsilateral kidney GFR decreased from baseline by 42% and 39% in the SF cohort, and by 45% and 62% in the MF cohort, at 12- and 24-months respectively (p-values < 0.03). The loss in renal function was 3.6±0.8% and 4.5±1.0% in the SF cohort, and 1.7±0.1% and 1.7±0.2% in the MF cohort, at 12- and 24-months respectively. The major loss in renal function occurred in high-dose regions, where dose-response curves converged to a plateau. ConclusionsFor the first time in a multicenter study, the dose-effect relationship at 12- and 24-months post-SABR treatment for primary RCC was quantified. Kidney function reduces linearly with dose up to 100 Gy BED3.

The Influence of Alkali Treatment and Multi Fraction Cantala Fiber Reinforced Carbon Nanotube Composite on Mechanical Properties and Morphological

The Influence of Alkali Treatment and Multi Fraction Cantala Fiber Reinforced Carbon Nanotube Composite on Mechanical Properties and Morphological

Profound DNA methylomic differences between single- and multi-fraction alpha irradiations of lung fibroblasts

BackgroundAlpha (α)-radiation is a ubiquitous environmental agent with epigenotoxic effects. Human exposure to α-radiation at potentially harmful levels can occur repetitively over the long term via inhalation of naturally occurring radon gas that accumulates in enclosed spaces, or as a result of a single exposure from a nuclear accident. Alterations in epigenetic DNA methylation (DNAm) have been implicated in normal aging and cancer pathogenesis. Nevertheless, the effects of aberrations in the methylome of human lung cells following exposure to single or multiple α-irradiation events on these processes remain unexplored.ResultsWe performed genome-wide DNAm profiling of human embryonic lung fibroblasts from control and irradiated cells using americium-241 α-sources. Cells were α-irradiated in quadruplicates to seven doses using two exposure regimens, a single-fraction (SF) where the total dose was given at once, and a multi-fraction (MF) method, where the total dose was equally distributed over 14 consecutive days. Our results revealed that SF irradiations were prone to a decrease in DNAm levels, while MF irradiations mostly increased DNAm. The analysis also showed that the gene body (i.e., exons and introns) was the region most altered by both the SF hypomethylation and the MF hypermethylation. Additionally, the MF irradiations induced the highest number of differentially methylated regions in genes associated with DNAm biomarkers of aging, carcinogenesis, and cardiovascular disease. The DNAm profile of the oncogenes and tumor suppressor genes suggests that the fibroblasts manifested a defensive response to the MF α-irradiation. Key DNAm events of ionizing radiation exposure, including changes in methylation levels in mitochondria dysfunction-related genes, were mainly identified in the MF groups. However, these alterations were under-represented, indicating that the mitochondria undergo adaptive mechanisms, aside from DNAm, in response to radiation-induced oxidative stress.ConclusionsWe identified a contrasting methylomic profile in the lung fibroblasts α-irradiated to SF compared with MF exposures. These findings demonstrate that the methylome response of the lung cells to α-radiation is highly dependent on both the total dose and the exposure regimen. They also provide novel insights into potential biomarkers of α-radiation, which may contribute to the development of innovative approaches to detect, prevent, and treat α-particle-related diseases.Graphical abstract

A Comparison of Single Fraction and Multi Fraction Radiosurgery on the Gamma Knife ICON: A Single Institution Review

PurposeBrain metastases are a common development in patients with malignant solid tumors. Stereotactic radiosurgery (SRS) has a long track record of effectively and safely treating these patients, with some limitations to the use of single fraction SRS based on size and volume. In this study, we reviewed outcomes of patients treated using SRS and fractionated SRS (fSRS) to compare predictors and outcomes of those treatments. Methods and MaterialsTwo hundred patients treated with SRS or fSRS for intact brain metastases were included. We tabulated baseline characteristics and performed a logistic regression to identify predictors of fSRS. Cox regression was used to identify predictors of survival. Kaplan-Meier analysis was used to calculate survival, local failure, and distant failure rates. A receiver operating characteristic curve was generated to determine timepoint from planning to treatment associated with local failure. ResultsThe only predictor of fSRS was tumor volume >2.061 cm3. There was no difference in local failure, toxicity, or survival by fractionation of biologically effective dose. Predictors of worse survival were age, extracranial disease, history of whole brain radiation therapy, and volume. Receiver operating characteristic analysis identified 10 days as potential factor in local failure. At 1 year, local control was 96.48 and 76.92% for those patients treated before or after that interval, respectively (P = .0005). ConclusionsFractionated SRS is a safe and effective alternative for patients with larger volume tumors not suitable for single fraction SRS. Care should be taken to treat these patients expeditiously as a delay was shown to affect local control in this study.

First experimental demonstration of VMAT combined with MLC tracking for single and multi fraction lung SBRT on an MR-linac

Background and purposeVMAT is not currently available on MR-linacs but could maximize plan conformality. To mitigate respiration without compromising delivery efficiency, MRI-guided MLC tumour tracking was recently developed for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) in combination with IMRT. Here, we provide a first experimental demonstration of VMAT + MLC tracking for several lung SBRT indications. Materials and methodsWe created central patient and phantom VMAT plans (8×7.5 Gy, 2 arcs) and we created peripheral phantom plans (3×18 & 1×34 Gy, 4 arcs). A motion phantom mimicked subject-recorded respiratory motion (A‾=11 mm, f‾=0.33 Hz, drift‾=0.3 mm/min). This was monitored using 2D-cine MRI at 4 Hz to continuously realign the beam with the target. VMAT + MLC tracking performance was evaluated using 2D film dosimetry and a novel motion-encoded and time-resolved pseudo-3D dosimetry approach. ResultsWe found an MLC leaf and jaw end-to-end latency of 328.05(±3.78) ms and 317.33(±4.64) ms, which was mitigated by a predictor. The VMAT plans required maximum MLC speeds of 12.1 cm/s and MLC tracking superimposed an additional 1.48 cm/s. A local 2%/1 mm gamma analysis with a static measurement as reference, revealed pass-rates of 28–46% without MLC tracking and 88–100% with MLC tracking for the 2D film analysis. Similarly, the pseudo-3D gamma passing-rates increased from 22–77% to 92–100%. The dose area histograms showed that MLC tracking increased the GTV D98% by 5–20% and the PTV D95% by 7–24%, giving similar target coverage as their respective static reference. ConclusionMRI-guided VMAT + MLC tracking is technically feasible on the MR-linac and results in highly conformal dose distribution.

Cost-Effectiveness of Single Versus Multifraction SABR for Pulmonary Oligometastases: The SAFRON II Trial

The use of stereotactic ablative body radiation therapy (SABR) in advanced cancer care is increasing, yet the cost-effectiveness of single-fraction (SF) versus multifraction (MF) SABR in pulmonary oligometastases is unknown. A prespecified cost-effectiveness analysis was conducted of the Trans Tasman Radiation Oncology Group 13.01 - SAFRON II - randomized trial comparing SF with MF SABR in 87 patients with 133 pulmonary oligometastases. A partitioned survival model assessed costs and quality-adjusted life-years (QALY) over the within-trial period (4 years) and longer-term (10 years). Costs reflected a societal perspective, expressed in Australian dollars (A$) using 2020 prices and were estimated using patient level data on health care utilization for radiation therapy (including patient time), post-radiation systemic therapy and treatment of adverse effects. Quality of life was assessed using the EuroQoL EQ-5D-5L. The incremental cost-effectiveness ratio (ICER) was expressed as the cost per QALY gained for SF versus MF SABR, with uncertainty assessed using deterministic and probabilistic sensitivity analyses. SF cost less than MF for initial therapy (difference of A$1194/patient). Mean time to initiation of systemic drug therapy did not differ between arms (P=.94). Numerical differences in survival favoring SF resulted in greater overall health care use for the within-trial period. The within-trial ICER was A$15,821/QALY and A$23,265/QALY over the longer term. Results were most sensitive to the cost of postprogression therapies and utility values. The sensitivity analysis indicated that SF SABR has a 97% probability of being cost-effective at a willingness-to-pay of A$50,000/QALY. SF has lower initial costs and is highly likely to be cost-effective. Time to initiation of systemic therapy associated with disease progression is highly patient relevant and is a major driver of cost-effectiveness. Comparisons for SF SABR with nonradiation therapy approaches to the treatment of pulmonary oligometastases warrant further investigation.

OC-0616 First VMAT delivery with MLC-tracking for single and multi fraction lung SBRT on a Unity MR-linac

OC-0616 First VMAT delivery with MLC-tracking for single and multi fraction lung SBRT on a Unity MR-linac

Radiation-induced Adaptive Response: New Potential for Cancer Treatment.

Radiotherapy is highly effective due to its ability to physically focus the treatment to target the tumor while sparing normal tissue and its ability to be combined with systemic therapy. This systemic therapy can be utilized before radiotherapy as an adjuvant or induction treatment, during radiotherapy as a radiation "sensitizer," or following radiotherapy as a part of combined modality therapy. As part of a unique concept of using radiation as "focused biology," we investigated how tumors and normal tissues adapt to clinically relevant multifraction (MF) and single-dose (SD) radiation to observe whether the adaptations can induce susceptibility to cell killing by available drugs or by immune enhancement. We identified an adaptation occurring after MF (3 × 2 Gy) that induced cell killing when AKT-mTOR inhibitors were delivered following cessation of radiotherapy. In addition, we identified inducible changes in integrin expression 2 months following cessation of radiotherapy that differ between MF (1 Gy × 10) and SD (10 Gy) that remain targetable compared with preradiotherapy. Adaptation is reflected across different "omics" studies, and thus the range of possible molecular targets is not only broad but also time, dose, and schedule dependent. While much remains to be studied about the radiation adaptive response, radiation should be characterized by its molecular perturbations in addition to physical dose. Consideration of the adaptive effects should result in the design of a tailored radiotherapy treatment plan that accounts for specific molecular changes to be targeted as part of precision multimodality cancer treatment.

The effect of different grain sizes and heat input on the gas pressure inside artificial resin-bonded sand cores

Sand cores are used to form the cavities of the castings. The quality of castings is directly affected by the quantity of the gases released from the cores. During our research, the effect of different grain sizes and heat input on the pressure of the gases evolved from the cores was investigated. The granulometric properties of the sand used for making the cores have a significant impact on the pressure of the gases. Because of the uneven particle size distribution of multi fraction sands, the gas flow conditions in the cores can be different. The gas pressure in the cores made from sieved sands can be changed between 6 and 9 mbar. According to the recorded cooling curve of the melt, it can be established, that in the case of the presented pouring conditions, a solid metal layer with adequate strength could not be developed before the gas could pass through the core/casting interface. This phenomenon may result in gas blowhole defects on the casting surface.

Single Fraction versus Multi Fraction Radiotherapy Treatment Schedules for Management of Painful Bone Metastasis

Single Fraction versus Multi Fraction Radiotherapy Treatment Schedules for Management of Painful Bone Metastasis

Results of an educational tool for residents and referring physicians on palliative radiation for bone metastases.

82 Background: Palliative radiation therapy (RT) for painful bone metastases is underutilized in the United States (U.S.), perhaps due to inappropriate use of multi-fraction (MF) regimens over more convenient, less costly, and equally effective single fraction (SF) regimens. Practice patterns may change with improved knowledge of radiation oncology residents (ROR) and non-radiation oncology physicians who refer patients for palliative RT. The aim of this study was to provide evidence-based educational content to these groups, and assess knowledge and views before and after. Methods: In April - June 2017, an electronic educational tool was sent to medical oncology and palliative care physicians, and ROR in the U.S. Multiple choice questions assessed knowledge, and were followed by evidence supporting the correct answer. Likert and sliding scales gaged tool impact. Chi-square and Mann-Whitney tests compared groups and pre/post-test responses. Results: Responses were obtained from 109 (2%) referring physicians (RP) and 135 (21%) ROR. ROR had higher scores than RP for 8 of 9 objective questions. RP were less likely to know that SF and MF are equivalent in terms of pain response (64 v. 91%, p &lt; 0.01) and subsequent analgesic use (86 v. 95%, p = 0.02), or that SF is associated with a higher retreatment rate (27 v. 93%, p &lt; 0.01). ROR were less likely to know that SF and MF are equivalent for patients with a high likelihood of long term survival (25 v. 56%, p &lt; 0.01). After viewing the content, ROR felt more knowledgeable [ mdn 3 (IQR 3 - 4) v. 4 (IQR 3 - 4), p &lt; 0.01], and RP felt more empowered [ mdn 3 (IQR 2 - 4) v. 4 (IQR 3 - 4), p &lt; 0.01]. RP found the survey more helpful, and knew less of the data prior [ mdn 50 (IQR 25 - 75%) v. 80% (IQR 66.3 - 90%), p &lt; 0.01]. Despite knowing the data, ROR preferred SF less than RP at completion (67 v. 85%, p &lt; 0.01). Conclusions: This study demonstrates a need for educational content for multidisciplinary providers on appropriate palliation of bone metastases. Despite ample knowledge, the bias of practicing radiation oncologists for MF is being passed onto residents. Greater knowledge may translate into more effective referral patterns and patient advocacy by RP, and potentially improve utilization of palliative RT in the U.S.

Patterns of practice in palliative radiotherapy for bone metastases in UK centres

AbstractBackgroundThere is abundant evidence of the comparative efficacy of single-fraction (SF) radiotherapy and multi-fraction (MF) radiotherapy when treating patients with bone metastases. Despite this, previous surveys have shown SF schedules to be underutilised.AimTo determine current patterns of practice in patients with bone metastasis and to investigate the factors that influence practice.MethodAn electronic audit was performed amongst 46 physicians, within 7 hospital trusts in the UK. The audit comprised of four hypothetical cases in which consultants and registrars chose which dose and fractionation they would recommend and their reasons for this recommendation.ResultsSF radiotherapy was the most common radiotherapy schedule in hypothetical cases 1, 3 and 4. SF radiotherapy was recommended by 65% of respondents in case 1, 47% in case 2, 89% in case 3 and 46% in case 4. For case 2, 50% proposed MF radiotherapy. For case 4, 22% of respondents recommended Stereotactic Body Radiotherapy (SABR). The following deciding factors were cited as influencing choice of an SF schedule: prognosis, published evidence, performance status and spinal cord compression.ConclusionThe most common radiotherapy schedule selected was SF. However, there were inter-institution differences regarding the use of SF radiotherapy. Furthermore, the survey had shown that a third of respondents recommended an MF regime, despite evidence supporting the efficacy of an SF schedule.

Single versus Multifraction Stereotactic Radiosurgery for Large Brain Metastases: An International Meta-analysis of 24 Trials

Multifraction (MF) stereotactic radiosurgery (SRS) purportedly reduces radionecrosis risk over single-fraction (SF) SRS in the treatment of large brain metastases. The purpose of the current work is to compare local control (LC) and radionecrosis rates of SF-SRS and MF-SRS in the definitive (SF-SRSD and MF-SRSD) and postoperative (SF-SRSP and MF-SRSP) settings. Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology guidelines were used to select articles in which patients had "large" brain metastases (Group A: 4-14cm3, or about 2-3cm in diameter; Group B: >14cm3, or about >3cm in diameter); 1-year LC and/or rates of radionecrosis were reported; radiosurgery was administered definitively or postoperatively. Random effects meta-analyses using fractionation scheme and size as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size and fractionation on the summary estimate, where the null hypothesis was rejected for P<.05. Twenty-four studies were included, published between 2008 and 2017, with 1887 brain metastases. LC random effects estimate at 1year was 77.6% for Group A/SF-SRSD and 92.9% for Group A/MF-SRSD (P=.18). LC random effects estimate at 1year was 77.1% for Group B/SF-SRSD and 79.2% for Group B/MF-SRSD (P=.76). LC random effects estimate at 1year was 62.4% for Group B/SF-SRSP and 85.7% for Group B/MF-SRSP (P=.13). Radionecrosis incidence random effects estimate was 23.1% for Group A/SF-SRSD and 7.3% for Group A/MF-SRSD (P=.003). Radionecrosis incidence random effects estimate was 11.7% for Group B/SF-SRSD and 6.5% for Group B/MF-SRSD (P=.29). Radionecrosis incidence random effects estimate was 7.3% for Group B/SF-SRSP and 7.5% for Group B/MF-SRSP (P=.85). Metaregression assessing 1-year LC and radionecrosis as a continuous function of increasing tumor volume was not statistically significant. Treatment for large brain metastases with MF-SRS regimens may offer a relative reduction of radionecrosis while maintaining or improving relative rates of 1-year LC compared with SF-SRS. These findings are hypothesis-generating and require validation by ongoing and planned prospective clinical trials.

Phase III Multi-Center, Prospective Randomized Trial Comparing High Dose Single Fraction Radiation Therapy to a 3-Fraction SBRT Regimen in the Treatment of Oligometastatic Human Cancer

Pre-clinical and clinical evidence have shown that high single dose radiation therapy (SDRT) is associated with superior tumor control compared to multi-fraction (MF) regimens, due to SDRT’s ability to engage a microvascular response interfering with the ability to repair radiation damage to tumor cell DNA. The primary objective of this study was to compare local control rates with either a single dose of 24Gy versus 27Gy in three 9Gy fractions in patients with oligometastatic disease. A secondary objective was to compare toxicity outcomes between the two cohorts. A total of 174 patients were enrolled at three institutions. 155 patients (75 randomized to the SDRT and 80 to the MF regimen) were assessable for treatment-related toxicities having met protocol criteria. A total of 117 patients with 154 treated lesions, were evaluable for the local disease control end point. Eligibility criteria for enrollment included ≤5 metastatic lesions documented on imaging studies, and no prior radiation therapy to the treated site. Eligible lesions were limited to non-mobile targets (osseous or lymph node metastases). Potential candidates whose target lesions were adjacent to critical organs, precluding treatment with SDRT due to the risk of treatment-induced complications, were excluded. Patients were followed every 6 months for a minimum of 2 years, and imaging evaluation of the treated site at 12 and 24 months post-treatment was mandatory. Responses were measured using standard RECIST criteria. For the assessment of toxicity, a minimum follow-up of 6 months was required. Median follow up was 39 months (range, 11-85). Lesions treated with SDRT demonstrated a significantly lower incidence of local disease progression (LR) compared to those treated with MF (p<0.0005). The 3-year incidence of LR was 6.1% of the lesions compared to 23% for the SDRT and MF regimens, respectively. A reduction in distant metastatic (DM) progression was noted among those treated with SDRT compared to the MF regimen The 3-year incidence of DM progression was 4.1% compared to 17.5% for the SDRT and MF regimens, respectively(p<0.02). There was no significant difference in grade 3+ toxicity between the two arms (SDRT: 10.7%; MF: 5%; p=0.24). The specific incidence of grade 3+ pain, peripheral neuropathy and bone fractures for the SDRT regimen was 5.3%, 2.7% and 1.3%. The corresponding incidence for these toxicities for the MF regimen was 1.3%, 0% and 2.5%. No overall survival differences were observed between the arms. The study provides Level 1 evidence that SDRT was associated with superior tumor control outcomes compared to a standard 3-fraction regimen in a cohort of patients with oligometastatic osseous/nodal disease. SDRT was well tolerated, rendering comparable toxicity outcomes to a current standard-of-care hypofractionated SBRT treatment regimen.

Abstract C146: Radiation-inducible molecular targets in a human prostate cancer mouse model

Abstract Background: In order to understand the changes induced in tumor cells following multi-fraction (MF) radiation therapy, we have previously studied molecular changes using prostate cancer cells and endothelial cells treated in vitro with MF doses of 0.5 Gy/1 Gy x 10 and 2 Gy x 5 and single-dose (SD) of 5 Gy and 10 Gy. The hypothesis being tested is that the response and adaptation to radiation-induced stress will produce a druggable phenotype. This might increase the utility of molecularly targeted therapeutics and also help address tumor cell heterogeneity. The data indicate more genes and pathways are induced by MF compared to SD and that the change in phenotype is more stable following MF. In this report, the focus is on new data from PC-3 cells irradiated in vivo and comparing it to MF and SD in vitro using MF 1 Gy x 10 and SD 10 Gy. Methods: PC-3 prostate cancer cells were implanted subcutaneously into the lateral aspect of rear leg of nude mice. Mice were divided into three groups (n = 3), based on radiation dose/schedule- control, SD, and MF. SD and MF employed similar dose/schedule as used for the in vitro studies, 10 Gy x 1 and 1 Gy x 10 respectively. RNA was isolated 24 h after radiation treatment. mRNA microarray analysis was performed using Agilent Technologies Human Gene Expression 4 × 44 K V2 microarrays. The data was generated and analyzed with GeneSpring® software (Agilent Technologies, Santa Clara, CA) and IPA software (IPA, QIAGEN, Redwood City, CA). Results: 6,374 genes were significantly altered by MF, with a cohort of genes, based on the &amp;gt; 250 gene ontology categories, involved in DNA response to stimulus, DNA repair, mitosis, cell cycle, and metabolism. In contrast, only 453 genes were significantly altered by SD, with ontological categories associated with cell morphology, assembly and organization such as actin filament-based process, extracellular matrix organization and biogenesis, fibril organization and biogenesis and collagen catabolism. Further bioinformatics analysis of the gene expression data with IPA, identified multiple pathways with functions correlated with the ontological categories. Significantly altered MF-induced genes are members of pathways which play a central role in DNA replication, recombination, and repair, cell proliferation and metabolism such as HIPPO Signaling, Protein Ubiquitination Pathway, JNK/SAPK Signaling, ERK/MAPK Signaling, G2/M DNA Damage Checkpoint Regulation, ATM Signaling, PI3K/AKT Signaling and Oxidative Phosphorylation. These pathways were uniquely up-regulated by MF treatment, as none of these changes were identified with SD radiation exposure. Conclusion: Our result show the differential expression pattern between SD and MF, with MF inducing changes in “targetable” molecular pathways. Ongoing studies: Currently we are in the process of evaluating radiation-induced targets in ATM signaling, DNA damage and repair, and multiple metabolic targets, and their potential for using radiation to prime cells for molecular-targeted drug therapy. Citation Format: Adeola Y. Makinde, Iris Eke, Molykutty J. Aryankalayil, Mansoor Ahmed, C. Norman Coleman. Radiation-inducible molecular targets in a human prostate cancer mouse model. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C146.

Adverse Outcomes After Palliative Radiation Therapy for Uncomplicated Spine Metastases: Role of Spinal Instability and Single-Fraction Radiation Therapy

Level I evidence demonstrates equivalent pain response after single-fraction (SF) or multifraction (MF) radiation therapy (RT) for bone metastases. The purpose of this study is to provide additional data to inform the incidence and predictors of adverse outcomes after RT for spine metastases. At a single institution, 299 uncomplicated spine metastases (without cord compression, prior RT, or surgery) treated with RT from 2008 to 2013 were retrospectively reviewed. The spinal instability neoplastic score (SINS) was used to assess spinal instability. The primary outcome was time to first spinal adverse event (SAE) at the site, including symptomatic vertebral fracture, hospitalization for site-related pain, salvage surgery, interventional procedure, new neurologic symptoms, or cord compression. Fine and Gray's multivariable model assessed associations of the primary outcome with SINS, SF RT, and other significant baseline factors. Propensity score matched analysis further assessed the relationship of SF RT to first SAEs. The cumulative incidence of first SAE after SF RT (n=66) was 6.8% at 30 days, 16.9% at 90 days, and 23.6% at 180 days. For MF RT (n=233), the incidence was 3.5%, 6.4%, and 9.2%, respectively. In multivariable analysis, SF RT (hazard ratio [HR] = 2.8, 95% confidence interval [CI] 1.5-5.2, P=.001) and SINS ≥ 11 (HR=2.5 , 95% CI 1.3-4.9, P=.007) were predictors of the incidence of first SAE. In propensity score matched analysis, first SAEs had developed in 22% of patients with SF RT versus 6% of those with MF RT cases (HR=3.9, 95% CI 1.6-9.6, P=.003) at 90 days after RT. In uncomplicated spinal metastases treated with RT alone, spinal instability with SINS ≥ 11 and SF RT were associated with a higher rate of SAEs.

The reimbursement system is not the dominant factor influencing reluctance to perform single-fraction radiotherapy for painful bone metastases.

Numerous prospective randomized controlled trials (RCTs) have demonstrated the equivalence of single-fraction (SF) and multi-fraction (MF) radiotherapy (RT) for the palliation of painful bone metastases (1-9). Recent practice guidelines support the use of SF-RT (10-13).

Radiation Survivors: Understanding and Exploiting the Phenotype following Fractionated Radiation Therapy

Radiation oncology modalities such as intensity-modulated and image-guided radiation therapy can reduce the high dose to normal tissue and deliver a heterogeneous dose to tumors, focusing on areas deemed at highest risk for tumor persistence. Clinical radiation oncology produces daily doses ranging from 1 to 20 Gy, with tissues being exposed to 30 or more daily fractions. Hypothesizing the cells that survive fractionated radiation therapy have a substantially different phenotype than the untreated cells, which might be exploitable for targeting with molecular therapeutics or immunotherapy, three prostate cancer cell lines (PC3, DU145, and LNCaP) and normal endothelial cells were studied to understand the biology of differential effects of multifraction (MF) radiation of 0.5, 1, and/or 2 Gy fraction to 10 Gy total dose, and a single dose of 5 and 10 Gy. The resulting changes in mRNA, miRNA, and phosphoproteome were analyzed. Significant differences were observed in the MF radiation exposures including those from the 0.5 Gy MF that produces little cell killing. As expected, p53 function played a major role in response. Pathways modified by MF include immune response, DNA damage, cell-cycle arrest, TGF-β, survival, and apoptotic signal transduction. The radiation-induced stress response will set forth a unique platform for exploiting the effects of radiation therapy as "focused biology" for cancer treatment in conjunction with molecular targeted or immunologically directed therapy. Given that more normal tissue is treated, albeit to lower doses with these newer techniques, the response of the normal tissue may also influence long-term treatment outcome.

&lt;b&gt;Mass concentrations and elemental composition of urban atmospheric aerosols in Addis Ababa, Ethiopia&lt;/b&gt;

Aerosol samples were collected from 22 February 2008 to 15 April 2008 and 17 June 2008 to 23 July 2008 in urban and peri-urban areas of Addis Ababa, Ethiopia, with the aim to assess the spatial and temporal aspects of total suspended particulate (TSP) and particulate matter with aerodynamic diameter less than 10 µm (PM10) and their composition in terms of metallic elements. Sixty six filter samples were collected from seven distinct sites using I.O.M. multi fraction dust samplers and fiber glass filter papers. The mass of each particulate matter sample was measured gravimetrically and the composition of PM10 samples was analyzed using ICP-OAES and SEM-EDAX. The concentration of TSP was in the range of 17-556 µg/m3 and that of PM10 was in the range of 17-285 µg/m3. The highest TSP and PM10 peak values were observed in February 2008 at two sites, whereas the lowest TSP and PM10 values were observed in June and July 2008 at two sites. The mean TSP concentration surpassed the WHO safe guideline value of 150 µg/m3 and 79 % of the PM10 values were below the WHO guideline value. The PM10 to TSP mass ratio was in the range 0.26-0.59 and PM10 mass contributed about 39% to the TSP mass. The average element concentration in PM10 filter sample was in the order of Ca > Na > K > Zn > Sb > B > Al > V > Mg > S > Fe. All the analyzed elements contributed about 0.1% to the PM10 mass. SEM-EDAX analysis of PM10 samples showed that Si, Al, Na, Zn, Ba, K and C were the predominant species. Crustal materials contributed 76-95% of the filter mass, and C and Cu represented 5-24%. The size distribution of aerosol particles as derived from SEM analysis was in 0.43-9.3 µm range. KEY WORDS: TSP, PM10, Metal analysis, Atmospheric aerosol, Addis Ababa, Ethiopia Bull. Chem. Soc. Ethiop. 2010, 24(3), 361-373.