Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer. PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0-2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1-2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov, NCT01584258. PACE-B recruitment is complete and follow-up is ongoing. Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference -1·9 percentage points, 95% CI -6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference -4·2 percentage points, 95% CI -10·0 to 1·7; p=0·16). No treatment-related deaths occurred. Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity. Accuray and National Institute of Health Research.

Background: Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. Methods: Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. Results: From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1–5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.

Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease.

We present a case report of chemotherapy induced renal salt wasting syndrome (RSWS) that was initially diagnosed and managed as syndrome of inappropriate secretion of antidiuretic hormone (SIADH), based on osmolality values as well as hydration status. The patient was receiving chemotherapy for metastatic testicular cancer. Progressive deterioration of electrolyte balance prompted the diagnosis of RSWS. This was confirmed by a high urinary sodium concentration, a simple but important investigation which is rarely requested in the initial investigation of hyponatraemia. Urine sodium concentration is high in RSWS but normal in SIADH. With chemotherapy playing such an important role in cancer management, the correct diagnosis of hyponatraemia in an oncology patient is vital in order to allow appropriate management. Although the distinctions between SIADH and RSWS can be very subtle, the management of these two distinct clinical situations is very different—namely, fluid restriction versus salt replacement.