Trends in the use of radiation therapy for stage IIA prostate cancer from 2004 to 2013: a retrospective analysis using the National Cancer Database.

BACKGROUND: Recent studies have shown a decrease in the overall use of radiation therapy in the treatment of prostate cancer over the past several decades, as well as a more conservative overall treatment approach. We aim to determine whether this trend continued from 2004 to 2013, and to determine whether there were changes in utilization for various types of radiation. METHODS: We conducted this retrospective study using the National Cancer Database. We identified 706 877 patients with sufficient treatment information diagnosed with stage IIA prostate cancer between 2004 and 2013. Logistic regression models were used to evaluate the yearly trend in radiation therapy utilization. RESULTS: There was a significant decline in the use of radiation therapy from 2004 to 2013, from 54.4% in 2004 to 34.5% in 2013 compared with all the other treatments. The use of external beam radiation therapy (EBRT) declined from 27.1% in 2004 to 25.0% in 2013, brachytherapy declined from 19.7% in 2004 to 6.1% in 2013, and combination therapy declined from 6.8% in 2004 to 2.6% in 2013. However, when considering only patients receiving radiation treatments, the use of EBRT steadily increased from 50.6% in 2004 to 74.0% in 2013, whereas the use of brachytherapy declined from 36.7% in 2004 to 18.2% in 2013. Finally, although the proportion of patients receiving combination radiation therapy initially declined from 2004 to 2009 (from 12.7 to 8.3%), there was little change in utilization from 2009 to 2013 (8.3 to 8.5%). CONCLUSIONS: There has been a significant decline in the use of overall radiation therapy, as well as for each radiotherapy modality, for the treatment of prostate cancer since 2004. For patients that are receiving radiation, the use of EBRT has increased while brachytherapy use has decreased. These data serve to encourage further analysis as to the causes of these trends and how they affect patient care.

Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma.

Follicular lymphoma exhibits intratumoral infiltration by non-malignant T lymphocytes, including CD4+CD25+ regulatory T (T(reg)) cells. We combined denileukin diftitox with rituximab in previously untreated, advanced-stage follicular lymphoma patients anticipating that denileukin diftitox would deplete CD25+ T(reg) cells while rituximab would deplete malignant B cells. Patients received rituximab 375 mg/m(2) weekly for 4 weeks and denileukin diftitox 18 mcg/kg/day for 5 days every 3 weeks for 4 cycles; neither agent was given as maintenance therapy. Between August 2008 and March 2010, 24 patients were enrolled. One patient died before treatment was given and was not included in the analysis. Eleven of 23 patients (48%; 95% confidence interval (CI): 27-69%) responded; 2 (9%) had complete responses and 9 (39%) had partial responses. The progression-free rate at 2 years was 55% (95%CI: 37-82%). Thirteen patients (57%) experienced grade ≥3 adverse events and one patient (4%) died. In correlative studies, soluble CD25 and the number of CD25+ T cells decreased after treatment; however, there was a compensatory increase in IL-15 and IP-10. We conclude that although the addition of denileukin diftitox to rituximab decreased the number of CD25+ T cells, denileukin diftitox contributed to the toxicity of the combination without an improvement in response rate or time to progression.

Controlled-release oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study.

Controlled-release oral formulations of oxycodone and morphine are both suitable analgesics for moderate to severe pain. They were compared in cancer-pain patients randomized to double-blind treatment with controlled-release oxycodone (n = 48) or controlled-release morphine (n = 52) every 12 h for up to 12 days. Stable analgesia was achieved by 83% of controlled-release oxycodone and 81% of controlled-release morphine patients in 2 days (median). Following titration to stable analgesia, pain intensity (0=none to 3=severe) decreased from baseline within each group (p

Steroids decrease granulocyte membrane fluidity, while phorbol ester increases membrane fluidity. Studies using electron paramagnetic resonance.

High concentrations of corticosteroids inhibit granulocyte responses and disrupt agonist receptor function. Dose-response and time-course considerations make it unlikely that these effects are mediated via the glucocorticoid receptor, a concept further supported by the ability of sex steroids to work similar effects. We postulated that steroids nonspecifically altered granulocyte membrane fluidity, which we measured directly by electron paramagnetic resonance. As predicted, methylprednisolone caused a dose-dependent increase in order parameter (decrease in fluidity) calculated on the basis of EPR spectra, using 5-doxylstearic acid (5-DS) as a probe of resting PMN membranes. This trend was highly significant (P less than 0.001; P at 0.5 mg/ml less than 0.01). Qualitatively similar results (but with different dose-response features) were obtained with conjugated estrogen. Granulocyte agonists (such as PMA) showed an opposite effect, which was not oxidatively mediated and which was steroid-inhibitable. 16-DS showed less prominent effects, suggesting that the membrane leaflets were more strongly affected than was the deep region of the membrane. Ibuprofen, which has similar effects to those of methylprednisolone on PMN aggregation and receptor function, caused a fluidizing rather than a stiffening of the membrane; this surprising result may indicate that there is a critical range of membrane fluidity for normal function, outside of which--in either direction--agonist receptor dysfunction occurs. We conclude that the immediate effects of very high doses of steroids are probably not mediated by corticoid receptors; instead, they may be due to changes in membrane fluidity.

Inhibition of granulocyte function by steroids is not limited to corticoids. Studies with sex steroids.

Noting that corticosteroid doses required for protection in shock models exceeded those required to saturate glucocorticoid receptors in mammalian cells, we postulated a nonspecific physicochemical effect of steroids upon the cell membrane, and therefore tested three noncorticoid steroids for their effects on granulocyte function. All three (conjugated equine estrogen, a synthetic progestogen, and a synthetic androgen) behaved in manner analogous to corticoids at similar concentrations, inhibiting granulocyte aggregation, chemotaxis, and chemiluminescence, as well as binding to the granulocytes of the synthetic oligopeptide agonist f-Met-Leu-Phe. Estrogen was further shown to reduce granulocyte membrane fluidity, assessed by electron paramagnetic resonance. We propose that the unique effects of extremely high-dose corticosteroids are not mediated via the glucocorticoid receptor, but result rather from physicochemical effects of the drugs upon the membranes of effector cells.

Hemophilic arthropathy complicated by polyarticular septic arthritis.

A case of multiple pyarthroses due to Staphylococcus aureus occurring in a severe classical hemophiliac is presented. Successful management depended on drainage of the infected joints and a prolonged course of antibiotics. Several criteria are suggested for recognition of hemophiliacs who might benefit from joint aspiration as a diagnostic tool for the presence of septic arthritis.