Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer : long-term survival results from the STAMPEDE trial

Background STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients. Methods We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional. Results Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P  0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression). Conclusions The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden

Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial

Background STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). Methods and findings Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. Conclusions Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. Trial registration ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544

Ecologia populacional dos Amphipoda (Crustacea) dos fitais de Caiobá, Matinhos, Paraná, Brasil Population ecolocy of Amphipoda (Crustacea) from the phytals of Caiobá, Matinhos, Paraná, Brazil

<abstract language="eng">Spalial and temporal density distributions of Amphipoda from the phytals of Caiobá are described. Air temperature oscillated from 16ºC (August and May) to 23ºC (March), surface water temperature from 17ºC (August) to 25ºC (March) and the salinity from 29.3‰ (May) to 32.8‰ (August). Two samples of 25cm² (for algae less than 5cm long), 100 cm² (for algae between 5-10cm long) and whole plants (for algae more than 10cm long) were removed with a spatula from the rocky surface at Caiobá Beach, in August/86, November/86, March/87 and May/87. After sorting, the algal substrata were weighted, their adsorption coefficient calculated and the sediment retained among the thallii weighted. The average distance between the branching was measured for all branched algae. The densities were calculated in relation to the weight of the algal substrate in grams. Eight phytals were considered: Ulva fasciata Delile, Padina gymnospora (Kútzing) Vickers, Sargassum cymosum Garth, Porphyra atropurpurea (Olivi) De Toni, Gelidium sp., Gymnogongrus griffithsiae (Turner) Martius, Pterocladia capillacea (Gmelin) Bornet &Thurel and Pterosiphonia pennata (Roth) Falkenberg, over which nine Amphipoda species live: Ampithoe ramondi Audouin, 1816, Cymadusa filosa Savigny, 1852, Elasmopus pectenicrus Bate, 1857, Hyale media Dana, 1857, Hyale sp.l, Jassa falcata Montagu, 1895 and Sunampithoe pelagica H. Milne-Edwards, 1830 (Gammaridea). Caprella danilevskii Czerniavski, 1861 and Caprella penantis Leach, 1814 (Caprellidea). Amphipoda densities ranged from 0.27 ind.g-1 to 45.68. ind.g-1. The broad-thallii algae Porphyra, Ulva and Padina harbored lower densities of Amphipoda, whereas those finely branched Pterocladia, Pterosiphonia and Gymnogongrus, the highest values and the less branched Sargassum and Gelidium, intermediate values. The high densities found in the finely branched algae had as main contribution the juvenile recruiting of most Amphipoda. The tide level might have influenced the temporal distribution of the Amphipoda density, due to the distinct time of air exposition in eaeh collection data. Most Amphipoda did not show specific algal substratum colonization: only Sunampithoe pelagica occurred solely in Sargassum. Four species occurred in different branched algae: J. falcata. S. pelagica. C. danilevskii and C. penantis. H. media had Sargassum, Pterocladia, Pterosiphonia and Gymnogongrus as the best algal substrata, whereas Caprellidea, the Pterocladia and Pterosiphonia phytals. High sediment weight in Padina was the main reason for high densities of Hyale sp.l in this phytal. The occurrence of males, females (including ovigerous ones) and juveniles of most Amphipoda species found in the present study indicates a complete life cycle whithin these phytals and corroborates with the assumption of the complexity of this marine coastal ecosystem