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Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10&#x202f;mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P&#x202f;=&#x202f;0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P&#x202f;=&#x202f;0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P&#x202f;<&#x202f;0.001). More patients in the targeted dose group achieved optimal ATG exposure (P&#x202f;=&#x202f;0.007) and superior CD4+ T-cell reconstitution (P&#x202f;=&#x202f;0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans

Identification and prognosis of low office and ambulatory blood pressure in patients with heart failure.

BACKGROUND: Low blood pressure (BP) limits the up-titration of guideline-directed medical therapies (GDMTs) and predicts poor outcomes in heart failure (HF). We assessed the value of ambulatory BP&#xa0;monitoring (ABPM) in detecting&#xa0;low BP and its impact on GDMTs optimization and prognosis in HF. METHODS: In&#xa0;491 HF patients initiating GDMTs from the Risk Evaluation and Management in Heart Failure (REM-HF) study since April 2018 to December 2022, ABPM was measured&#xa0;in addition to office BP. Participants were classified as sustained low systolic BP (SBP) (24-hour and office SBP < 120&#x2009;mmHg), masked low SBP (24-hour SBP < 120&#x2009;mmHg, office SBP &#x2265; 120&#x2009;mmHg), and no low SBP. The primary outcome was a composite of all-cause mortality and HF rehospitalization. GDMTs target dose achievement was assessed at 3 months. Logistic regression and&#xa0;Cox regression models were used to assess GDMTs optimization and outcomes across SBP groups. RESULTS: Sustained, masked, and no low SBP were observed in 25.3%, 30.8%, and 44.0% of patients, respectively. Both sustained (OR 2.36, 95%CI 1.25-4.47) and masked low SBP (OR 2.32, 95%CI 1.11-4.87) groups were associated with lower likelihood of achieving GDMTs target doses. Over a median 21-month follow-up, all-cause mortality and HF rehospitalization rates were higher in sustained (HR 2.45, 95% CI 1.56-3.86) and masked low SBP (HR 1.68, 95% CI 1.08-2.62) groups. No difference was found in the target dose achievement and outcomes between the two low SBP groups. CONCLUSION: Sustained and masked low SBP were common in HF and both associated with GDMTs intolerance and adverse outcomes.

Humans

Studies in dose-time-volume relationships in bladder and tongue radium implants.

The clinical results of 26 tongue and 31 bladder radium implants were analysed in terms of proposed dose specification parameters that describe the dose-time-volume relationships of the implant. Tongue cases that recurred within two years were mostly those with a relatively short treatment time and in which a relatively large dose reduction factor had to be applied. The dose-time factor did not differ significantly in the groups of bladder implants having different clinical results. A higher incidence of necrosis was noted in bladder cases. This was associated with a significantly higher mean dose and a somewhat greater degree of dose inhomogeneity. Recurrences were generally linked with greater mean dose, target volume and dose inhomogeneity. These unfavourable dose-volume relationships were frequently associated with poor distribution of needles. The reported experimental and clinical findings pertinent to the differential sparing of normal tissues associated with protraction of continuous irradiation are outlined. In the light of these, it is felt that the results of tongue implants could have been improved by omission of the dose-time adjustment factor for treatment time of 3-10 days without undue risk of necrosis. However, bladder results could have been improved by attainment of a better implantation technique while keeping the treatment time within 6-8 days in view of the lower tolerance.

Carcinoma, Squamous Cell

Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF.

BACKGROUND: Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy. OBJECTIVES: In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial. METHODS: In FINEARTS-HF, patients with an eGFR of 25 to 60&#x2009;mL/min/1.73&#x2009;m2 at baseline were stratified at randomization to the low-dose group and started on 10&#x2009;mg of finerenone once daily (titrated to a maximum 20&#x2009;mg/d) or matching placebo, whereas those with an eGFR >60&#x2009;mL/min/1.73&#x2009;m2 at baseline were stratified to the high-dose group and started on 20&#x2009;mg of finerenone once daily (titrated to a maximum 40&#x2009;mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death. RESULTS: Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean &#xb1; SD achieved dose was 32.3&#x2009;&#xb1;&#x2009;9.1&#x2009;mg (finerenone) and 34.4&#x2009;&#xb1;&#x2009;7.8&#x2009;mg (placebo) in the higher eGFR/high-dose stratum, and 15.6&#x2009;&#xb1;&#x2009;4.3&#x2009;mg (finerenone) and 16.7&#x2009;&#xb1;&#x2009;4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01). CONCLUSIONS: In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25&#x2009;mL/min/1.73&#x2009;m2. We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptitration to the target dose to ensure optimal therapeutic outcomes. (FINEARTS-HF [Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%; NCT04435626).

Aged

The correct dose: pharmacologically guided end point for anti-growth factor therapy.

Strategies to block the effects of tumor growth factors, such as estrogen, and to recruit other regulatory elements, such as with retinoids, have focused interest on the possibility of successful tumor intervention approaches. Approaches that neutralize the effects of critical molecules that drive tumor promotion are attractive targets for evaluation as new intervention agents. Clinical intervention trials with early stage patients or with subjects from "high risk" populations impose stricter types of constraints than conventional chemotherapy approaches in advanced stage patients. The potential for short-term toxicity has to be considered, as it may affect subject accrual or compliance. The longer expected survival of intervention subjects mandates closer attention to the possibilities of unexpected long-term toxicities with chronic administration of an intervention agent. As part of a Phase I clinical trial evaluating the utility of a monoclonal antibody directed against the autocrine growth factor, gastrin-releasing peptide to block the growth of small cell lung cancer, we developed a mathematical model to predict the requisite amount of antibody to neutralize growth factor effect. This model requires knowledge of the equilibrium concentration of the secreted growth factor, specific receptor, and bioavailability of the antibody in the tumor interstitium. A range of possible target doses of antibody can be developed to address the potential for heterogeneity frequently encountered in such systems, including a range of levels for peptide production and specific receptor expression. This approach could be applied to rationally derive treatment or intervention in which specific information regarding the relevant binding parameters is available. Through refinement of this modeling approach more context-specific dosing of agonist/antagonists could be determined which may decrease side effects associated with the drug administration.

Antibodies, Monoclonal

Clinical Outcomes and Patient Experiences With Celiprolol Therapy in Vascular Ehlers-Danlos Syndrome: The First Non-European Cohort.

Vascular Ehlers-Danlos syndrome (vEDS) is a hereditary connective tissue disorder caused by heterozygous pathogenic variants in COL3A1. European studies have shown that celiprolol may reduce the risk of life-threatening vascular events, but outcomes in non-European populations and the therapy's psychological impact remain unclear. We conducted a retrospective cohort study of individuals aged &#x2265;&#x2009;20&#x2009;years with genetically confirmed vEDS in a single referral center in Japan between 2000 and 2024. Clinical, molecular, and treatment data were obtained from medical records, and semi-structured interviews were conducted with a subset of participants to assess patient experiences. Twenty-six patients were included. The mean age at celiprolol initiation was 36.9&#x2009;years, with a mean follow-up of 96.6&#x2009;months. All patients received celiprolol, and 61.5% reached the target dose (400&#x2009;mg/day). One patient died of hepatic artery rupture; vascular events occurred in 11, while 14 remained event-free. No significant associations were observed between vascular event occurrence and genotype or celiprolol dose. Interviews with 11 patients revealed that celiprolol use provided emotional reassurance and promoted a more proactive approach to disease management. Celiprolol therapy may reduce fatal vascular events in vEDS and have a positive psychological impact, though nonfatal vascular complications remain frequent.

Humans

X-ray therapy of primary bone tumors.

Radiotherapy of bone tumors can now be performed exclusively by megavolt therapy. Giant cell tumors hsould be resected. If the lesion is not completely resectable, surgery should be followed by the administration of a target dose of 3000 rads in 4-6 weeks. Inoperable giant cell tumors are irradiated to a tumor dose of 5000 rads, inoperable giant cell tumors of grade III receive a dose of 8000 rads as do osteosarcomas. Ewing's sarcoma and reticulum cell sarcoma can be totally destroyed by a tumor dose of 6000 rad with sufficient reliability. Combination with chemotherapy may offer a chance of improvement. Osteosarcoma should be resected. If surgery is too late (early distant metastases), a tumor dose of 8000 to 10000 rads would be able to destroy the tumor cells. Histologic control investigations have proved this.

Bone Neoplasms

Finerenone and Cardiovascular Outcomes According to Baseline Kidney Function in Patients With Heart Failure: The FINEARTS-HF Trial.

BACKGROUND: Finerenone is known to reduce the risk of worsening heart failure (HF) events and cardiovascular (CV) death in patients with HF with mildly reduced or preserved ejection fraction. OBJECTIVES: The authors explored whether the benefit of finerenone among patients with HF with mildly reduced or preserved ejection fraction differs according to baseline measures of kidney function. METHODS: FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) was a global, randomized clinical trial of finerenone vs placebo among patients with HF with mildly reduced or preserved ejection fraction. Finerenone was titrated to 20 mg/d if the estimated glomerular filtration rate (eGFR) was &#x2264;60 mL/min/1.73 m2 or 40 mg/d if eGFR was >60 mL/min/1.73 m2. The authors used a semiparametric proportional rates method, stratified by left ventricular ejection fraction (<60%; &#x2265;60%) and region, to assess for differential treatment effects on the composite of total HF events and CV death according to the baseline eGFR (continuous and categories [&#x2265;60 mL/min/1.73 m2, 45 to <60 mL/min/1.73 m2, <45 mL/min/1.73 m2] and urine albumin-creatinine ratio (UACR) (<30 mg/g, 30 to <300 mg/g, &#x2265;300 mg/g). RESULTS: The effect of finerenone to reduce the primary endpoint of total HF events and CV death did not significantly differ according to baseline eGFR (Pinteraction = 0.14 and 0.07 for continuous and categorical eGFR, respectively) with rate ratio 0.72 (95% CI: 0.59-0.88) for eGFR &#x2265;60 mL/min/1.73 m2, 0.83 (95% CI: 0.65-1.06) for eGFR 45 to <60 mL/min/1.73 m2, and 1.02 (95% CI: 0.83-1.26) for eGFR <45 mL/min/1.73 m2. The corresponding absolute event rates were 9.2 vs 12.5, 16.5 vs 19.9, and 28.0 vs 28.0 per 100 patient-years for finerenone vs placebo, respectively. Similar results were noted for total worsening HF events. Finerenone lowered the risk of the composite CV outcome similarly across baseline categories of UACR (Pinteraction = 0.48). CONCLUSIONS: In the FINEARTS-HF trial (where the target dose of finerenone was determined by baseline kidney function), the effect of finerenone to reduce the composite of cardiovascular death and total HF events did not significantly differ across a range of baseline eGFR and UACR.

Humans

Risk assessment of urban air pollution.

Urban air pollution, originating in western countries mainly from automotive engine exhausts, contains thousands of components, many of which are genotoxic, i.e. are putative cancer initiators. Other pollution components, such as NO2 and certain particles, may have cocarcinogenic/promotive effects, at least at higher exposure levels. Cancer risk assessment of this complex mixture has to combine data from the exposure history, from epidemiological studies as well as from animal carcinogenicity tests, and from in vitro studies of fractions and individual components. Data for metabolism and pharmaco-kinetics have also to be considered. A multiplicative linear model is assumed to be valid for cancer initiation at low levels. Attempts are being made to determine the target dose from ultimate carcinogens (reactive metabolites) via macromolecule adduct levels, and to base the risk assessment on the radiation-dose equivalent to the chemical dose. So far this has been possible only for simple alkenes, which are metabolized to epoxides, and indirectly, via benzo(a)pyrene (BaP), for particle-bound polycyclic aromatic hydrocarbons (PAH). The lifetime risk of cancer (all sites) from ethene is estimated accordingly to 1.4 x 10(-4) per microgram m-3, and from PAH to 12 x 10(-4) per ng m-3 BaP. For other components indicated to give risk contribution (NOx, volatile PAH, benzene, aldehydes, butadiene) essential data are lacking and only very rough estimates can be given at this time.

Air Pollutants

[Homogenization of the dose to the target volume in case of irregular body-surface by means of compensation (author's transl)].

Irregular body-surface contours in the treatment part of high-energetic photon fields are producing an inhomogeneous dose distribution within the target volume. Homogenization of the dose is necessary in order to avoid over- or underdosage. A technique of making compensators is described. These are individual compensation filters substituting tissue layers which are lacking, they are correctly scaled down and optimally corrected in view of absorption and scattering according to the actual irradiation conditions. A simple mechanical device makes possible the production of a mould for heavy-metal compensators immediately in the course of scanning of the body-surface. A universal semi-automatic version of this method is appropriate to clinical practice; it records optically, and therefore without contact and quickly, all body-contours desired. By means of the image of moiré contour-lines thus obtained can be made the mould for the compensator in a second operation using an electronically controlled copy-milling machine.

Filtration

Unequal weighting of given doses in opposed fields in treatment of cancer of the tonsillar region using 60Co, 4-, 8-, 15-, 24-MVp photons.

Weighting of given doses from parallel opposed fields is a widespread practice in radiation therapy of cancer in the tonsillar region. In order to determine when weighting is useful, dose distributions on the central axis were calculated for various energies (60Co, 4-, 8-, 15-, and MVp photons), weighting factors, and field separations. Criteria for judging the usefulness of weighting were (i) that variation in the dose across the tumor volume not exceed 10%, and (ii) that the dose to critical tissues outside the target volume be at least 20% less than target volume dose. The clinical situation that met these criteria was a lateral lesion that extended to less than one-third of the transverse diameter of the head, treated with either 60Co, 8, or 4 MVp with 4:1 weighting. Under these conditions, weighting was considered to be justified.

Cobalt Radioisotopes

[Practice of computer use in radiotherapy planning].

The main problems of radiotherapy planning are discussed with respect to use of computers now being available for a greater number of centers. One of the most essential premises is apart from clear ideas on a modern target volume concept - a sufficiently high speed in producing realistic summarized isodose contours for any radiation therapy arrangement in any individual patient's cross section outline. This problem being solved, those individual summarized isodose figures have to be critically evaluated and therefore the importance of applicable meaningful optimization criteria come into account. The properties of such criteria, which must be quantifiable, generally applicable and really relevant for judgement on quality of a plan, had to be accepted, before automatic optimization procedures could be developed; principles involved are presented. By means of a short series of examples, namely 60Co fixed field combinations with and without use of wedges, combinations of arc therapy for a number of clinical tasks. It has been pointed out, that most experienced estimate by the eye would have been by far insufficient when compared to the automized computer optimization when using such simple criteria as 1. homogeneity of absorbed dose within target volume, 2. numerically limited absorbed dose within areas of risk, 3. as low as possible radiation effects to all "outside areas". It seems to be a real danger, that so called isodose libraries, how high their merits might be estimated, may change into an "isodose bcemetery", unless we'll be successful for each individual clinical case by use of computers, which are now prepared to supply the best possible variant of the standard plan or the primary radiotherapy idea. Regular use of computers in such a way will furthermore give an incomparable documentation material.

Breast Neoplasms

Performance of a gas target neutron source for radiotherapy.

The performance of a compact and efficient neutron generator, using the 3H(d, n) reaction and a gas target, is reported. The target is formed in a windowless, differentially pumped vessel pressurised to 7.5 Torr. An extended source of 15 MeV neutrons is produced when the target is bombarded by a 10 mA beam of 210 keV deuterons. Measurements are reported of the neutron energy spectra, neutron and gamma-ray dose rates, target lifetime and tritium handling. The neutron flux distribution of the extended target was measured and compared with the predictions of a simple beam-gas interaction model. The measured neutron source strength is 1.7 +/- 0.4 X 10(12) neutrons per second. The source output is limited by target beam current, not target power considerations.

Deuterium

Absorbed radiation dose from radionuclidic impurities in several 123I-labeled radiopharmaceuticals.

The radiation dose to patients from RISA, sodium iodohippurate, and rose bengal labeled with commercially available 123I and its accompanying radioimpurities has been studied. The extra radiation dose to target organs was found to range from 29% to 97% that due to 123I alone when the radiopharmaceutical is administered at calibration time. Additional delay in the time of administration increases the relative impurity dose.

Drug Contamination

Effect of cell division inhibitors on polyclonal activation can vary according to the target cell used.

The effects of inhibitors of cell division on polyclonal stimulation induced either by bacterial lipopolysaccharide (LPS) or by a synthetic adjuvant, MDP, were compared, using different target cells. Doses of colchicine that prevented 3H-thymidine incorporation also prevented the induction of antibodies against TNP and against an altered self antigen: bromelain-treated mouse red blood cells (br-MRBC). Under identical conditions, incubation with cytosine arabinoside (CA) strongly prevented the induction of anti-TNP PFC and to a lesser degree anti-SRBC PFC. However, the number of anti br-MRBC PFC was unchanged even when a dose of CA which inhibits totally the incorporation of 3H-thymidine was used. Our findings indicate that the general term "polyclonal stimulation" may concern at least two different types of cell populations and therefore we strongly stress the importance of choosing similar targets in comparative experiments.

Acetylmuramyl-Alanyl-Isoglutamine

Radiation-induced inhibition of RNA synthesis in Tetrahymena pyriformis.

Radiation-induced disturbances in RNA synthesis were investigated in exponentially growing Tetrahymena. Sub-lethal doses of gamma-radiation lead to a transient, dose-dependent decrease in the rate of total RNA synthesis measured by 3H-uridine incorporation, without an alteration of 3H-uridine uptake by the cells. The rate of 3H-uridine incorporation decreases exponentially with dose. In contrast, the duration of inhibition of RNA synthesis is linearly dependent on dose. Target-theory calculations suggest that the sensitive molecule has a molecular weight of about 2 X 10(7) Daltons.

Animals

High-dose radiotherapy in patients with high-risk prostate cancers treated with long-term androgen deprivation therapy (GETUG AFU 18): a randomised, phase 3 trial.

BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9&#xb7;5 years (IQR 8&#xb7;5-10&#xb7;3), 5-year progression-free survival was 91&#xb7;4% (95% CI 87&#xb7;0-94&#xb7;4) in the dose-escalation group versus 88&#xb7;1% (83&#xb7;2-91&#xb7;6) in the control group, and 10-year progression-free survival was 83&#xb7;6% (77&#xb7;8-88&#xb7;0) versus 72&#xb7;2% (65&#xb7;3-78&#xb7;0; stratified HR 0&#xb7;56, 95% CI 0&#xb7;40-0&#xb7;78, p<0&#xb7;0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING: French National Cancer Institute and AstraZeneca.

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