Summary Background Androgen-deprivation therapy is offered to men with prostate cancer who have a rising prostate-specific antigen after curative therapy (PSA relapse) or who are considered not ...suitable for curative treatment; however, the optimal timing for its introduction is uncertain. We aimed to assess whether immediate androgen-deprivation therapy improves overall survival compared with delayed therapy. Methods In this randomised, multicentre, phase 3, non-blinded trial, we recruited men through 29 oncology centres in Australia, New Zealand, and Canada. Men with prostate cancer were eligible if they had a PSA relapse after previous attempted curative therapy (radiotherapy or surgery, with or without postoperative radiotherapy) or if they were not considered suitable for curative treatment (because of age, comorbidity, or locally advanced disease). We used a database-embedded, dynamically balanced, randomisation algorithm, coordinated by the Cancer Council Victoria, to randomly assign participants (1:1) to immediate androgen-deprivation therapy (immediate therapy arm) or to delayed androgen-deprivation therapy (delayed therapy arm) with a recommended interval of at least 2 years unless clinically contraindicated. Randomisation for participants with PSA relapse was stratified by type of previous therapy, relapse-free interval, and PSA doubling time; randomisation for those with non-curative disease was stratified by metastatic status; and randomisation in both groups was stratified by planned treatment schedule (continuous or intermittent) and treatment centre. Clinicians could prescribe any form and schedule of androgen-deprivation therapy and group assignment was not masked. The primary outcome was overall survival in the intention-to-treat population. The trial closed to accrual in 2012 after review by the independent data monitoring committee, but data collection continued for 18 months until Feb 26, 2014. It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000301561) and ClinicalTrials.gov ( NCT00110162 ). Findings Between Sept 3, 2004, and July 13, 2012, we recruited 293 men (261 with PSA relapse and 32 with non-curable disease). We randomly assigned 142 men to the immediate therapy arm and 151 to the delayed therapy arm. Median follow-up was 5 years (IQR 3·3–6·2) from the date of randomisation. 16 (11%) men died in the immediate therapy arm and 30 (20%) died in the delayed therapy arm. 5-year overall survival was 86·4% (95% CI 78·5–91·5) in the delayed therapy arm versus 91·2% (84·2–95·2) in the immediate therapy arm (log-rank p=0·047). After Cox regression, the unadjusted HR for overall survival for immediate versus delayed arm assignment was 0·55 (95% CI 0·30–1·00; p=0·050). 23 patients had grade 3 treatment-related adverse events. 105 (36%) men had adverse events requiring hospital admission; none of these events were attributable to treatment or differed between treatment-timing groups. The most common serious adverse events were cardiovascular, which occurred in nine (6%) patients in the delayed therapy arm and 13 (9%) in the immediate therapy arm. Interpretation Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention in men with PSA-relapsed or non-curable prostate cancer. The results provide benchmark evidence of survival rates and morbidity to discuss with men when considering their treatment options. Funding Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia.
Stereotactic ablative radiotherapy (SABR) has emerged as an effective, noninvasive alternative to surgery in patients with oligometastatic disease. Historically, select patients with adrenal ...oligometastases have been treated with adrenalectomies which can offer durable local control and reasonable survival rates. SABR is a promising noninvasive treatment alternative to surgery capable of delivering ablative doses of radiation to the tumor with the goal of achieving durable local control of adrenal metastases. We report on a case of a patient who underwent initial surgical resection for a locally advanced lung adenocarcinoma and subsequently developed an early, biopsy-proven, oligometastatic recurrence in the adrenal gland. He underwent chemotherapy and SABR using CyberKnife to the adrenal metastasis and is in remission 7 years after treatment with no late toxicity. Fractionated SABR is an attractive noninvasive alternative to surgery for adrenal metastases. This case demonstrates that select patients with adrenal oligometastases, can achieve long-term remission and even cure following SABR.
Radiosurgery (RS) can offer excellent local control in the management of both benign and malignant tumors measuring less than 3 cm in size. A known late complication of radiosurgery is radiation ...necrosis which generally occurs within 6-18 months following treatment and has an increased risk of occurrence with higher radiation doses. The lower dose used to treat vestibular schwannomas (VS) makes this complication less frequent. Tumors that do not respond to radiosurgery and continue to grow may require surgical intervention. We report a case of a young male who received radiosurgery (18 Gy in 3 fractions) in February 2016 for a recurrent VS following initial debulking surgery in 2008. Follow-up imaging revealed an interval decrease in size by May 2017; however, by April 2018, there was significant interval increase in the cisternal components of the tumor. By September 2018, the lesion had increased by >50% (to a size of 29 mm) compared to May 2017. The patient agreed to undergo repeat surgical debulking. Upon review of the preoperative MRI, the cisternal component of the tumor had substantially decreased in size. Although uncommon, this reflects delayed, pseudoprogression which, in our case, was self-limiting. This raises a question regarding when to proceed with surgical intervention of growing VS following radiosurgery given the potential for delayed resolution of radiation necrosis and demonstrates a gap in our current literature involving surgery of VS following radiosurgery.
The dramatic rise in the use of contrast agents for diagnostic imaging within the last decade has largely contributed to the effectiveness of MR imaging, however even with the use of prophylaxis, ...adverse reactions to contrast, including anaphylaxis, still occur. We describe the case of a 46-year-old female patient with a hemangiopericytoma requiring ongoing contrast MR surveillance, and a documented anaphylactic reaction to Gadovist (gadobutrol injection) despite premedication. Allergy testing was positive to intradermal undiluted Gadovist, confirming an IgE-mediated Gadovist allergy, with subsequent skin testing by prick and intradermal negative to undiluted MultiHance. She went on to receive MultiHance prior to her subsequent MRI scans without clinical reaction and without premedication, demonstrating that there may be superior alternatives to traditionally used gadolinium dyes in patients with moderate to severe reactions, and warrants further investigation into the anaphylactoid characteristics between the different gadolinium-based contrast agents.
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