Background Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. Methods In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. Results In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P = 0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P = 0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P = 0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. Conclusions The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

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Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

https://www.europeanurology.com/article/S0302-2838(07)01145-1/pdf/eau-guidelines-on-prostate-cancer

EAU guidelines on prostate cancer

EAU–ESTRO–SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent

https://www.europeanurology.com/article/S0302-2838(13)01040-3/pdf/eau-guidelines-on-prostate-cancer-part-1-screening-diagnosis-and-local-treatment-with-curative-intent-update-2013

EAU Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent—Update 2013

INTRODUCTION The postmortem observations of Green, published in the Lancet in 1836, were the fi rst to describe the distinct pathological features of tuberculous meningitis and set it apart from the other recognised causes of ‘acute hydrocephalus’ (Green 1836). The challenge for the physician then lay in distinguishing the disease before death, and delivering the grave prognosis. Thomas Mann captures the full horror of this process in Dr Faustus as the helpless Dr Kurbis presides over the agonizing death of a small child from tuberculous meningitis: The whole thing lasted scarcely two weeks, including the earliest signs that all was not quite well with the child; from the beginnings no one – I believe no one at all – even dreamed of the horror to come ... Kurbis tested the child’s eyes, the pupils of which were tiny and showed a tendency to squint. The pulse raced. Muscular contractions developed, and an incipient rigidity of the neck. It was cerebrospinal meningitis, infl ammation of the meninges. The good man pronounced the name with a deprecating movement of the head shoulderwards, probably in the hope that they might not know the almost complete powerlessness of medical science in the face of this onslaught. Tuberculous meningitis was invariably fatal before the advent of anti-tuberculosis chemotherapy. Therefore, the need to diagnose the disorder became a priority after streptomycin was found to reduce mortality of tuberculous meningitis by one third in 1948 (MRC 1948). Progress was rapid over the next 5 years: adding para-aminosalicylic acid to streptomycin reduced mortality to 30%, and the addition of isoniazid to both of these compounds lowered the mortality still more to Robert Koch: photograph taken in the 1880s, around the time of his discovery of the tubercle bacillus (or ‘bacille Koch’, as it is still called in Vietnam).

The diagnosis and management of

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)09408-4.pdf

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.

http://ruirodrigues.pt/braqui/braqui_prostata.pdf

ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer.

Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy.

Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs.

/pdf/a-randomized-controlled-trial-of-orbital-radiotherapy-versus-4cl5qn29wr.pdf

Leo E.C.M. Blank

Papers

Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.

ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer.

Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy.

A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy.

Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study