Factors affecting the use of single-fraction radiotherapy for the palliation of bone metastases in Australia.

AIMS: Palliative radiotherapy for bone metastases remains an important treatment in patients with metastatic malignancy. Previous studies have indicated a reluctance to adopt single-fraction treatment despite considerable evidence. This study aims to describe the factors determining the use of palliative radiotherapy in patients with bone metastases and assess whether fractionation patterns have changed over time with emerging evidence. MATERIALS AND METHODS: A retrospective review of radiotherapy databases at Liverpool/Macarthur Cancer Therapy Centre and the Royal Brisbane and Women's Hospital was conducted for the period 1997-2009. Patients receiving palliative radiotherapy for bony metastases were identified and treatment sites were grouped into 'spine', 'limb', 'multiple' or 'other'. Treatment courses were divided into single- or multiple-fraction treatments. The effects of socioeconomic and geographical factors on radiotherapy utilisation and fractionation were assessed. RESULTS: In total, 5683 patients were identified in the cohort; they received a total of 8211 bone treatments. The overall proportion of single-fraction radiotherapy was 29%, with significant variation over the study period (P < 0.001). Age under 70 years and spine or multiple treatment sites were all associated with lower usage of single-fraction radiotherapy on multivariate analysis. Prostate and lung primary sites were associated with higher usage of single-fraction treatment. The proportion of single-fraction treatment remained low (35%), even for patients who survived less than 22 days from their last treatment. Socioeconomic and geographical factors had little effect on the number of fractions used. CONCLUSIONS: The rate of single-fraction radiotherapy for bone metastases has remained low in two large Australian institutions, despite considerable evidence that single-fraction treatment provides equivalent pain relief to fractionated therapy. This trend towards fractionated treatment was largely maintained, even in patients with limited life expectancy. Further measures to increase the rate of single-fraction therapy are needed.

Patterns of retreatment by radiotherapy.

AIMS: To describe patterns of treatment for those who receive more than one episode of megavoltage radiotherapy (retreatment) by cancer type for better service planning and benchmarking. MATERIALS AND METHODS: Institutional databases of all patients who received their first megavoltage radiotherapy for any type of cancer at the Liverpool and Macarthur Cancer Therapy Centres (LM), New South Wales, Australia, Royal Brisbane and Women's Hospital (RBWH), Queensland, Australia and Radiotherapeutic Institution Friesland (RIF), Leeuwarden, the Netherlands, over the period 1991-2009 were examined. Radiotherapy retreatment was defined as any radiotherapy episode, to any body site, after an initial episode of radiotherapy, for the same cancer diagnosis. The total retreatment rate was defined as the number of retreatment episodes of radiotherapy divided by the number of cases in the cohort. RESULTS: In total, 62,270 patients (RBWH 38581, LM 9654, RIF 14035) received 77,762 episodes of radiotherapy, giving a total retreatment rate of 0.25; 52,351 patients (84%) received only one episode of treatment and 9919 (16%) received two or more episodes of treatment. Overall retreatment rates for LM, RBWH and RIF were 0.24, 0.25 and 0.26, respectively. For the five most common cancer types treated, the median time between treatment episodes was longest for breast cancer (11.3 months), then head and neck cancer (9.7 months), colorectal cancer (7.2 months), prostate cancer (4.4 months) and lung cancer (4.1 months). Ninety-one per cent of all fractions were delivered in the first episode of treatment. CONCLUSIONS: The retreatment rate was very similar between the three facilities, suggesting agreement about the indications for retreatment.

Occult metastatic intestinal adenocarcinoma resulting in pathological fracture of the proximal humerus.

Intestinal adenocarcinomas are rare but have been described in the literature. The present case is unusual in both its clinical presentation and in the distribution of metastatic lesions. The sequestrum formation and pathological fracture present are most commonly associated with osteomyelitis in horses and the details of the case highlight the need for differential diagnosis in these particular circumstances and of which clinicians should be aware.

Effect of a bioflavonoid dietary supplement on acetaminophen-induced oxidative injury to feline erythrocytes.

OBJECTIVE: To determine the effect of a commercial bioflavonoid antioxidant on acetaminophen-induced oxidative injury to feline erythrocytes. DESIGN: Randomized controlled study. ANIMALS: 45 healthy age-matched cats. PROCEDURE: Cats were assigned to 3 experimental groups. Groups 1 and 3 received a bioflavonoid antioxidant (10 mg/d) orally for 2 weeks. Groups 2 and 3 received an oxidative challenge with acetaminophen (90 mg/kg [41 mg/lb] of body weight, PO) on day 7. Packed cell volume, percentage of erythrocytes with Heinz bodies, blood methemoglobin concentration, and blood reduced and oxidized glutathione concentrations were determined at various times during the 2-week study period. RESULTS: Adverse effects were not associated with bioflavonoid antioxidant administration alone. Acetaminophen administration resulted in a significant increase in methemoglobin concentration in groups 2 and 3; differences were not detected between these groups. Heinz body concentrations in groups 2 and 3 increased after acetaminophen administration; however, the increase in cats that received the antioxidant was significantly less than in group-2 cats. Total blood glutathione concentrations did not change significantly in groups 2 and 3 after acetaminophen administration; however, ratio of reduced to oxidized glutathione concentration increased significantly after administration in group-2 cats, compared with group-3 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of bioflavonoid antioxidants to cats at risk for oxidative stress may have a beneficial effect on their ability to resist oxidative injury to erythrocytes.

Cloning of the xynB gene from Dictyoglomus thermophilum Rt46B.1 and action of the gene product on kraft pulp.

A two-step PCR protocol was used to identify and sequence a family 11 xylanase gene from Dictyoglomus thermophilum Rt46B.1. Family 11 xylanase consensus fragments (GXCFs) were amplified from Rt46B.1 genomic DNA by using different sets of consensus PCR primers that exhibited broad specificity for conserved motifs within fungal and/or bacterial family 11 xylanase genes. On the basis of the sequences of a representative sample of the GXCFs a single family 11 xylanase gene (xynB) was identified. The entire gene sequence was obtained in the second step by using genomic walking PCR to amplify Rt46B.1 genomic DNA fragments upstream and downstream of the xynB GXCF region. The putative XynB peptide (M(r), 39,800) encoded by the Rt46B.1 xynB open reading frame was a multidomain enzyme comprising an N-terminal catalytic domain (M(r), 22,000) and a possible C-terminal substrate-binding domain (M(r), 13,000) that were separated by a short serine-glycine-rich 23-amino-acid linker peptide. Seven xylanases which differed at their N and C termini were produced from different xynB expression plasmids. All seven xylanases exhibited optimum activity at pH 6.5. However, the temperature optima of the XynB xylanases varied from 70 to 85 degrees C. Pretreatment of Pinus radiata and eucalypt kraft-oxygen pulps with XynB resulted in moderate xylan solubilization and a substantial improvement in the bleachability of these pulps.

Metabolic abnormalities in feline Niemann-Pick type C heterozygotes.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal storage disorder in which cholesterol lipidosis results from defective intracellular transport of unesterified cholesterol. The primary molecular defect of NPC is unknown; regulatory mechanisms of cholesterol metabolism are impaired, resulting in retarded esterification of exogenous cholesterol with accumulation of unesterified cholesterol in lysosomes and secondary storage of glycolipids and sphingomyelin. In obligate heterozygotes from a feline NPC model, cultured skin fibroblasts challenged with exogenously derived cholesterol exhibited intermediate rates of cholesterol esterification and accumulation of unesterified cholesterol. Liver lipid analyses of obligate heterozygote cats demonstrated intermediate cholesterol and sphingomyelin concentrations. Vacuolated skin fibroblasts were found in 2 of 3 heterozygote cats, and occasional cortical neurons exhibited intracellular inclusions immunoreactive for GM2-ganglioside. Ultrastructural studies provided evidence of storage in liver and brain. We believe these morphological and biochemical findings are the first example of manifestations of CNS abnormalities in a genetic carrier for a neuronal storage disease.

Localization and treatment of familial malignant nonfunctional paraganglioma with iodine-131 MIBG: report of two cases.

Two cases of familial, malignant, nonfunctional paraganglioma are reported. Uptake of iodine-131 metaiodobenzylguanidine ([131I]MIBG) by the tumors and metastases was demonstrated. In the first case, with multicentric and locally invasive disease, [131I]MIBG correctly localized a right carotid body paraganglioma which had been missed arteriographically. In the second case, with widespread, symptomatic metastatic disease, a therapeutic dose of [131I]MIBG produced palliation of bone pain after the failure of radio- and chemotherapy. Uptake of [131I]MIBG by paragangliomas does not correlate with catecholamine secretory activity. Iodine-131 MIBG should be considered as a therapeutic option in unresectable, malignant paragangliomas which take up this radiopharmaceutical.

Response to aminoglutethimide after tamoxifen therapy in advanced breast cancer.

We describe sequential response to aminoglutethimide after eventual failure of treatment with tamoxifen in a patient with metastatic breast cancer. We suggest that aminoglutethimide is the next logical hormone therapy for such patients.