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IntroductionTOBAS is a pragmatic study that includes 2 randomized trials and embedded prospective registries of treated or conservatively managed patients.Aim of StudyWe report the results of the stereotactic radiosurgery (SRS) registry in TOBAS. For patients considered for curative treatment, clinicians select the primary curative method and whether observation is a reasonable alternative.Method1010 patients were recruited in TOBAS; 105 (10.4%) were included in the SRS registry. After exclusions, 94 patients remained for analysis. Most had ruptured (68%), small AVMs (0–3 cm) (89%), within eloquent brain (61%). Pre-SRS embolization was performed in 19/94 (20%) and was curative in 4.ResultsThree other patients had complications, leaving 87/94 (93%) patients who actually received SRS. The median SRS dose administered was 22 Gy (IQR 20–24). During a mean clinical follow-up of 51 months, the primary outcome (mRS>2) occurred in 7/94 (7%; 95%CI:4%-15%), and serious adverse events related to the AVM or AVM treatment occurred in 16/94 (15%). AVM rupture occurred in 5/94 (5%; 95%CI:2%-12%), all re-ruptures, and symptomatic radiation-induced changes in 6/94 (6%; 95%CI:2%-13%). Three-year imaging follow-up, available in 79/94 (84%) confirmed AVM occlusion in 51/79 (66%) or 54% (95%) of all patients.ConclusionIn this prospective registry of ruptured and unruptured brain AVMs, radiosurgery was relatively safe, but of moderate efficacy, with ruptures during follow-up in 5% and documented AVM occlusion in 54% of patients at 3 years.Conflict of InterestNo

The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions. This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0–1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1–3 vs 4–5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744. 99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19–54) in the control group versus 26 months (23–37) in the SABR group. Median overall survival was 28 months (95% CI 19–33) in the control group versus 41 months (26–not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30–1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5–34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group. SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit. Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.

Abstract BACKGROUND Stereotactic radiosurgery (SRS) for benign intracranial meningiomas is an established treatment. OBJECTIVE To summarize the literature and provide evidence-based practice guidelines on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS Articles in English specific to SRS for benign intracranial meningioma, published from January 1964 to April 2018, were systematically reviewed. Three electronic databases, PubMed, EMBASE, and the Cochrane Central Register, were searched. RESULTS Out of the 2844 studies identified, 305 had a full text evaluation and 27 studies met the criteria to be included in this analysis. All but one were retrospective studies. The 10-yr local control (LC) rate ranged from 71% to 100%. The 10-yr progression-free-survival rate ranged from 55% to 97%. The prescription dose ranged typically between 12 and 15 Gy, delivered in a single fraction. Toxicity rate was generally low. CONCLUSION The current literature supporting SRS for benign intracranial meningioma lacks level I and II evidence. However, when summarizing the large number of level III studies, it is clear that SRS can be recommended as an effective evidence-based treatment option (recommendation level II) for grade 1 meningioma.

A randomized trial showed noninferiority of stereotactic body radiotherapy to conventionally or moderately hypofractionated radiotherapy in preventing biochemical recurrence in selected men with localized prostate cancer.

SummaryBackgroundStereotactic ablative body radiotherapy (SABR) is increasingly being used to treat oligometastatic cancers, but high-level evidence to provide a basis for policy making is scarce. Additional evidence from a real-world setting is required. We present the results of a national study of patients with extracranial oligometastases undergoing SABR, representing the largest dataset, to our knowledge, on outcomes in this population so far. MethodsIn 2015, National Health Service (NHS) England launched a Commissioning through Evaluation scheme that funded a prospective, registry-based, single-arm, observational, evaluation study of patients with solid cancer and extracranial oligometastases treated with SABR. Prescribed doses ranged from 24–60 Gy administered in three to eight fractions. The study was done at 17 NHS radiotherapy centres in England. Patients were eligible for the scheme if aged 18 years or older with confirmed primary carcinoma (excluding haematological malignancies), one to three extracranial metastatic lesions, a disease-free interval from primary tumour development to metastases of longer than 6 months (with the exception of synchronous colorectal liver metastases), a WHO performance status of 2 or lower, and a life expectancy of at least 6 months. The primary outcome was overall survival at 1 year and 2 years from the start of SABR treatment. The study is now completed. FindingsBetween June 15, 2015, and Jan 30, 2019, 1422 patients were recruited from 17 hospitals in England. The median age of the patients was 69 years (IQR 62–76), and the most common primary tumour was prostate cancer (406 [28·6%] patients). Median follow-up was 13 months (IQR 6–23). Overall survival was 92·3% (95% CI 90·5–93·9) at 1 year and 79·2% (76·0–82·1) at 2 years. The most common grade 3 adverse event was fatigue (28 [2·0%] of 1422 patients) and the most common serious (grade 4) event was increased liver enzymes (nine [0·6%]). Notreatment-related deaths were reported. InterpretationIn patients with extracranial oligometastatic cancer, use of SABR was associated with high overall survival and low toxicity. ’The study findings complement existing evidence from a randomised, phase 2 trial, and represent high-level, real-world evidence supporting the use of SABR in this patient cohort, with a phase 3 randomised, controlled trial to confirm these findings underway. Based on the selection criteria in this study, SABR was commissioned by NHS England in March, 2020, as a treatment option for patients with oligometastatic disease. FundingNHS England Commissioning through Evaluation scheme.

Background and objectiveThe optimal management of large vestibular schwannomas continues to be debated. We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of this problem from a European perspective.Material and methodsA systematic review of MEDLINE database, in compliance with the PRISMA guidelines, was performed. A subgroup analysis screening all surgical series published within the last 20 years (January 2000 to March 2020) was performed. Weighted summary rates for tumor resection, oncological control, and facial nerve preservation were determined using meta-analysis models. This data along with contemporary practice patterns were discussed within the task force to generate consensual recommendations regarding preoperative evaluations, optimal surgical strategy, and follow-up management.ResultsTumor classification grades should be systematically used in the perioperative management of patients, with large vestibular schwannomas (VS) defined as > 30 mm in the largest extrameatal diameter. Grading scales for pre- and postoperative hearing (AAO-HNS or GR) and facial nerve function (HB) are to be used for reporting functional outcome. There is a lack of consensus to support the superiority of any surgical strategy with respect to extent of resection and use of adjuvant radiosurgery. Intraoperative neuromonitoring needs to be routinely used to preserve neural function. Recommendations for postoperative clinico-radiological evaluations have been elucidated based on the surgical strategy employed.ConclusionThe main goal of management of large vestibular schwannomas should focus on maintaining/improving quality of life (QoL), making every attempt at facial/cochlear nerve functional preservation while ensuring optimal oncological control, thereby allowing to meet patient expectations. Despite the fact that this analysis yielded only a few Class B evidences and mostly expert opinions, it will guide practitioners to manage these patients and form the basis for future clinical trials.

Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0–2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70–82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7–5·5). All patients enrolled had T1–T2a and N0–N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38–60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

IntroductionRadiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) is increasing in the treatment of brain metastases (BMs). Aim of the present study was to evaluate the safety and effectiveness of SRS/SFRT for BMs, using a new mono-isocenter non-coplanar solution (HyperArc™ Varian Medical System).MethodsBMs patients with a diameter inferior to 3 cm, a life expectancy of more than 3 months and a good performance status, were eligible for Linac-based volumetric modulated arc therapy (VMAT) SFRT/SRS with HyperArc™. A retrospective analysis of patients and BMs was performed.ResultsFrom August 2017 to May 2018, 381 BMs in 64 patients were treated and 246 BMs (43 patients, median number of BMs: 5) of them were suitable for analysis. With a median FU time of 6 months, 244 out 246 (99%) BMs were controlled (18% complete response; 41% partial response, 40% stable disease), 2 BMs showed a progression, at the first control. No acute or late toxicities were reported. Median overall survival (OS) has not yet been achieved, while median time to progression was 5 months. In univariate analysis, statistically negative prognostic factors for OS were histology of primary tumor (p = 0.009): lung/breast cancer had better survival rates as compared to others. Cumulative intracranial volume disease ≥ 15 cc and systemic progression disease were independent prognostic factors for OS at univariate (p = 0.04; p = 0.005) and multivariate (p = 0.04; p = 0.009) analysis, respectively.ConclusionThe present first clinical data show that SFRT/SRS with HyperArc™ is safe and effective for BMs patients. The utilization of SFRT/SRS for BMs is promising and should be further explored in randomized trials.

Moderately hypofractionated radiotherapy (MHRT) is a standard treatment for prostate cancer. Stereotactic body radiotherapy (SBRT) is also effective, and has been shown to be non-inferior to MHRT in a lower-risk group of patients who did not require hormone therapy (PACE-B), but randomised data on toxicity for higher-risk patients are lacking. We aimed to compare the early toxicity of MHRT and SBRT. The randomised, open-label, phase 3, non-inferiority PACE-C trial, conducted at 53 hospitals across the UK, Republic of Ireland, and New Zealand, recruited men aged at least 18 years with intermediate-risk or high-risk histologically confirmed prostate adenocarcinoma (T1–T3a, Gleason 7–8, and prostate specific antigen 10–30 ng/mL) and with WHO performance status of 0–2. Participants were centrally randomly assigned (1:1; non-masked; permuted block size of four and six; stratified by centre and risk group) to MHRT (60 Gy; 20 daily fractions over 4 weeks) or SBRT (36·25 Gy; five daily or alternate day fractions; over 1–2 weeks) with an additional mandatory clinical target volume dose target of 40 Gy (no margin) to the prostate, and proximal 1 cm of seminal vesicles. 6 months of androgen deprivation therapy was planned and was started before commencement of radiotherapy. The primary outcome of PACE-C is freedom from biochemical or clinical failure, the data for which are not yet mature. The co-primary endpoints for this preplanned safety analysis were the percentages of Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicities at any point during or within 12 weeks of completion of radiotherapy (the early or acute period). Analyses are by treatment received, with participants included if they had one or more fractions of MHRT or SBRT, regardless of their allocated treatment. Late toxicity and efficacy data are awaited as the trial remains in follow-up. The study was prospectively registered with ClinicalTrials.gov, NCT01584258. Between Nov 13, 2019, and June 24, 2022, 1208 participants were randomly assigned (601 to MHRT and 607 to SBRT). 608 patients received MHRT and 584 received SBRT, and thus were included in the study analysis. 1136 (95%) of 1192 patients were White, 20 (2%) were Black or Black British, 17 (1%) were Asian or Asian British, and seven (1%) were Chinese or other. During the early period (within 12 weeks of treatment), the co-primary endpoint of RTOG grade 2 or worse genitourinary toxicity was observed in 166 (27%) of 608 patients (95% CI 23·8 to 31·1) receiving MHRT and 162 (28%) of 582 patients (24·3 to 31·7) after SBRT (absolute difference 0·5%, 95% CI –4·7 to 5·7; p=0·89). For grade 2 or worse genitourinary Common Terminology Criteria for Adverse Events (CTCAE), 170 (28%) of 604 patients had events after MHRT and 195 (34%) of 581 patients had events after SBRT (p=0·050). Grade 3 CTCAE genitourinary toxicity was observed in three (<1%) patients receiving MHRT and three (1%) patients receiving SBRT. For grade 2 or worse gastrointestinal CTCAE, 60 (10%) of 604 patients had an event after MHRT and 96 (17%) of 581 patients had an event after SBRT (p=0·0011). Grade 3 CTCAE gastrointestinal toxicity was observed in three (<1%) patients receiving MHRT and four (1%) patients receiving SBRT. During the early period, the co-primary endpoint of RTOG grade 2 or worse gastrointestinal toxicity was observed in 69 (11%) of 608 patients (95% CI 9·0 to 14·2) receiving MHRT and 74 (13%) of 584 patients (10·2 to 15·8) receiving SBRT (absolute difference 1·4%, 95% CI –2·5 to 5·2; p=0·53). There were no treatment-related deaths. Despite an accelerated treatment schedule and a larger treated volume than PACE-B, SBRT and MHRT had similar rates of early RTOG toxicity. The Royal Marsden Cancer Charity.

Localised prostate cancer is commonly treated with external beam radiotherapy and moderate hypofractionation is non-inferior to longer schedules. Stereotactic body radiotherapy (SBRT) allows shorter treatment courses without impacting acute toxicity. We report 2-year toxicity findings from PACE-B, a randomised trial of conventionally fractionated or moderately hypofractionated radiotherapy versus SBRT. PACE is an open-label, multicohort, randomised, controlled, phase 3 trial conducted at 35 hospitals in the UK, Ireland, and Canada. In PACE-B, men aged 18 years and older with a WHO performance status 0–2 and low-risk or intermediate-risk histologically-confirmed prostate adenocarcinoma (Gleason 4 + 3 excluded) were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group to control radiotherapy (CRT; 78 Gy in 39 fractions over 7·8 weeks or, following protocol amendment on March 24, 2016, 62 Gy in 20 fractions over 4 weeks) or SBRT (36·25 Gy in five fractions over 1–2 weeks). Androgen deprivation was not permitted. Co-primary outcomes for this toxicity analysis were Radiation Therapy Oncology Group (RTOG) grade 2 or worse gastrointestinal and genitourinary toxicity at 24 months after radiotherapy. Analysis was by treatment received and included all patients with at least one fraction of study treatment assessed for late toxicity. Recruitment is complete. Follow-up for oncological outcomes continues. The trial is registered with ClinicalTrials.gov, NCT01584258. We enrolled and randomly assigned 874 men between Aug 7, 2012, and Jan 4, 2018 (441 to CRT and 433 to SBRT). In this analysis, 430 patients were analysed in the CRT group and 414 in the SBRT group; a total of 844 (97%) of 874 randomly assigned patients. At 24 months, RTOG grade 2 or worse genitourinary toxicity was seen in eight (2%) of 381 participants assigned to CRT and 13 (3%) of 384 participants assigned to SBRT (absolute difference 1·3% [95% CI –1·3 to 4·0]; p=0·39); RTOG grade 2 or worse gastrointestinal toxicity was seen in 11 (3%) of 382 participants in the CRT group versus six (2%) of 384 participants in the SBRT group (absolute difference –1·3% [95% CI –3·9 to 1·1]; p=0·32). No serious adverse events (defined as RTOG grade 4 or worse) or treatment-related deaths were reported within the analysis timeframe. In the PACE-B trial, 2-year RTOG toxicity rates were similar for five fraction SBRT and conventional schedules of radiotherapy. Prostate SBRT was found to be safe and associated with low rates of side-effects. Biochemical outcomes are awaited. Accuray.