Corrigendum to “Palaeohydrogeology and Transport Parameters Derived from 4He and Cl Profiles in Aquitard Pore Waters in a Large Multilayer Aquifer System, Central Australia”

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.In the article titled “Palaeohydrogeology and Transport Parameters Derived from 4 He and Cl Profiles in Aquitard Pore Waters in a Large Multilayer Aquifer System, Central Australia” [1], Mr. Stanley D. Smith was missing from the authors’ list. Mr. Stanley made a significant contribution in helping with the core sampling protocol, canister leak testing, and discussing modelling methods. The corrected authors’ list is shown above

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Palaeohydrogeology and Transport Parameters Derived from 4He and Cl Profiles in Aquitard Pore Waters in a Large Multilayer Aquifer System, Central Australia

A study of chloride and 4He profiles through an aquitard that separates the Great Artesian Basin from the underlying Arckaringa Basin in central Australia is presented. The aquitard separates two aquifers with long water residence times, due to low recharge rates in the arid climate. One-dimensional solute transport models were used to determine the advective flux of groundwater across the aquitard as well as establish any major changes in past hydrological conditions recorded by variations of the pore water composition. This in situ study showed that both diffusion and slow downward advection (vz=0.7 mm/yr) control solute transport. Numerical simulations show that an increase in chloride concentration in the upper part of the profile is due to a reduction in recharge in the upper aquifer for at least 3000 years. Groundwater extraction since 2008 has likely increased chloride and 4He concentrations in the lower aquifer by pulling up water from deeper layers; however, there has been insufficient time for upward solute transport into the pore water profile by diffusion against downward advection. The transport model of 4He and chloride provides insight into how the two aquifers interact through the aquitard and how climate change is being recorded in the aquitard profile

Detecting inter-aquifer leakage in areas with limited data using hydraulics and multiple environmental tracers, including He-4, Cl-36/Cl, C-14 and Sr-87/Sr-86

The investigation of regionally extensive groundwater systems in remote areas is hindered by a shortage of data due to a sparse observation network, which limits our understanding of the hydrogeological processes in arid regions. The study used a multidisciplinary approach to determine hydraulic connectivity between the Great Artesian Basin (GAB) and the underlying Arckaringa Basin in the desert region of Central Australia. In order to manage the impacts of groundwater abstraction from the Arckaringa Basin, it is vital to understand its connectivity with the GAB (upper aquifer), as the latter supports local pastoral stations and groundwater-dependent springs with unique endemic flora and fauna. The study is based on the collation of available geological information, a detailed analysis of hydraulic data, and data on environmental tracers. Enhanced inter-aquifer leakage in the centre of the study area was identified, as well as recharge to the GAB from ephemeral rivers and waterholes. Throughout the rest of the study area, inter-aquifer leakage is likely controlled by diffuse inter-aquifer leakage, but the coarse spatial resolution means that the presence of additional enhanced inter-aquifer leakage sites cannot be excluded. This study makes the case that a multi-tracer approach along with groundwater hydraulics and geology provides a tool-set to investigate enhanced inter-aquifer leakage even in a groundwater basin with a paucity of data. A particular problem encountered in this study was the ambiguous interpretation of different age tracers, which is attributed to diffusive transport across flow paths caused by low recharge rates.ISSN:1431-2174ISSN:1435-015

Ubiquitous karst hydrological control on speleothem oxygen isotope variability in a global study

Speleothem oxygen isotopic (δ18O) records are used to reconstruct past hydroclimate yet records from the same cave do not always replicate. We use a global database of speleothem δ18O to quantify the replicability of records to show that disagreement is common worldwide, occurs across timescales and is unrelated to climate, depth or lithology. Our global analysis demonstrates that within-cave differences in mean speleothem δ18O values are consistent with those of dripwater, supporting a ubiquitous influence of flowpaths. We present a case study of four new stalagmite records from Golgotha Cave, southwest Australia, where the isotopic differences between them are informed by cave monitoring. It is demonstrated that karst hydrology is a major driver of within-cave speleothem and dripwater δ18O variability, primarily due to the influence of fractures on flowpaths. Applying our understanding of water movement through fractures assists in quantitative reconstruction of past climate variability from speleothem δ18O records

δ13C and δ18O record of Stalagmite GL-S2 from the Golgotha Cave in southwest Western Australia

GolgothaCave_GLS2_stalagmite_O&C_isotopes: median depth, d18O and d13C values in VPDB. Chronology is that used for Treble et al (2022)