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Stereotactic ablative body radiotherapy (SABR) is a non-invasive treatment option for primary renal cell carcinoma, for which long-term data are awaited. The primary aim of this study was to report on long-term efficacy and safety of SABR for localised renal cell carcinoma. This study was an individual patient data meta-analysis, for which patients undergoing SABR for primary renal cell carcinoma across 12 institutions in five countries (Australia, Canada, Germany, Japan, and the USA) were eligible. Eligible patients had at least 2 years of follow-up, were aged 18 years or older, had any performance status, and had no previous local therapy. Patients with metastatic renal cell carcinoma or upper-tract urothelial carcinoma were excluded. SABR was delivered as a single or multiple fractions of greater than 5 Gy. The primary endpoint was investigator-assessed local failure per the Response Evaluation Criteria in Solid Tumours version 1.1, and was evaluated using cumulative incidence functions. 190 patients received SABR between March 23, 2007, and Sept 20, 2018. Single-fraction SABR was delivered in 81 (43%) patients and multifraction SABR was delivered in 109 (57%) patients. Median follow-up was 5·0 years (IQR 3·4–6·8). 139 (73%) patients were men, and 51 (27%) were women. Median age was 73·6 years (IQR 66·2–82·0). Median tumour diameter was 4·0 cm (IQR 2·8–4·9). 96 (75%) of 128 patients with available operability details were deemed inoperable by the referring urologist. 56 (29%) of 190 patients had a solitary kidney. Median baseline estimated glomerular filtration rate (eGFR) was 60·0 mL/min per 1·73 m2 (IQR 42·0–76·0) and decreased by 14·2 mL/min per 1·73 m2 (IQR 5·4–22·5) by 5 years post-SABR. Seven (4%) patients required dialysis post-SABR. The cumulative incidence of local failure at 5 years was 5·5% (95% CI 2·8–9·5) overall, with single-fraction SABR yielding fewer local failures than multifraction (Gray's p=0·020). There were no grade 3 toxic effects or treatment-related deaths. One (1%) patient developed an acute grade 4 duodenal ulcer and late grade 4 gastritis. SABR is effective and safe in the long term for patients with primary renal cell carcinoma. Single-fraction SABR might yield less local failure than multifraction, but further evidence from randomised trials is needed to elucidate optimal treatment schedules. These mature data lend further support for renal SABR as a treatment option for patients unwilling or unfit to undergo surgery. None.

Iris melanoma is a rare form of uveal melanoma with potential metastic spread. Treatment options include surgical resection, enucleation or irradiation. We analysed visual outcome, complication appearance and management in eight patients with iris melanoma following robotic-assisted CyberKnife treatment. Consecutive patients from the Department of Ophthalmology at University of Munich were included in the study if they had an iris melanoma that was treated with CyberKnife and had a minimum follow-up of 12 months. We evaluated tumor thickness, largest diameter, visual acuity and complications. 8 patients were included in this report. The median age was 74 years (range: 53–86 years). The median follow-up was 23 months (range 12–48 months). Tumor thickness decreased from 2.1 to 1.4 mm on average. Four out of eight patients showed stable or increased visual acuity compared to visual acuity at first visit. We did not find a correlation of applied radiation volume or radiation dose on visual outcome. Radiation keratopathy was the most common complication in five patients. No recurrences were noted. Robotic-assisted radiosurgery following CyberKnife is a promising non-invasive, single session treatment option for iris melanoma with comparable results regarding recurrence rate or complications to brachytherapy and proton beam therapy. All included patients showed good visual outcome.

Key Points Conventional radiotherapy has a limited role in the treatment of renal cell carcinoma (RCC), and is largely limited to the palliation of symptoms of metastatic disease Evolving technology has facilitated the safe delivery of ablative doses of radiotherapy, in fewer fractions, and has been increasingly adopted in the clinical management of patients Preclinical and clinical evidence demonstrates that RCC is sensitive to ablative doses of radiation (typically ≥8 Gy per fraction), with tumour control rates of approximately 90% High-dose radiation seems to have an immunogenic effect in patients with RCC, and might explain the abscopal effects sometimes observed with this approach Combinations of ablative radiotherapy with systemic targeted therapies or immunotherapies are promising approaches that might improve outcomes Renal cell carcinoma (RCC) is largely percieved to be radioresistant, owing to the failure of several clinical trials involving fractionated radiotherapy. However, following the availability of new technologies, which enable the delivery of ablative doses of radiation, in fewer fractions, excellent responses have been observed among patients with RCC. In this Review, the authors describe the evidence supporting the use of ablative-dose radiotherapy, either alone, or in combination with other therapies in patients with RCC. Conventional radiotherapy previously had a limited role in the definitive treatment of renal cell carcinoma (RCC), owing to the disappointing outcomes of several trials and the perceived radioresistance of this type of cancer. In this context, radiotherapy has been relegated largely to the palliation of symptoms in patients with metastatic disease, with variable rates of response. Following the availability of newer technologies that enable safe delivery of high-dose radiotherapy, stereotactic ablative radiotherapy (SABR) has become increasingly used in patients with RCC. Preclinical evidence demonstrates that RCC cells are sensitive to ablative doses of radiotherapy (≥8–10 Gy). Trials in the setting of intracranial and extracranial oligometastases, as well as primary RCC, have demonstrated excellent tumour control using this approach. Additionally, an awareness of the capacity of high-dose radiation to stimulate antitumour immunity has resulted in novel combinations of SABR with immunotherapies. Here we describe the historical application of conventional radiotherapy, the current biological understanding of the effects of radiation, and the clinical evidence supporting the use of ablative radiotherapy in RCC. We also explore emerging opportunities to combine systemic targeted agents or immunotherapies with radiation. Radiotherapy, although once an overlooked approach, is moving towards the forefront of RCC treatment.

The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.

PurposeChoroidal metastases occur in many patients with systemic cancer and limit quality of life due to visual deterioration or pain. The limited prognosis of these patients demand treatment approaches that aim at a quick response and easy application. We evaluated a robotic assisted radiosurgery device, the CyberKnife, in the treatment of choroidal metastasis.MethodsFollowing retrobulbar anaesthesia, target volume was defined by an interdisciplinary team using gadolinium-contrast-enhanced MRI, computer tomography (CT) as well as all previously obtained clinical data. Radiation was delivered in a single fraction with a CyberKnife at a radiation dose of 21 Gy with a 70% isodose. We evaluated tumour height, reflectivity, visual acuity and side effects over the course of the follow-up.ResultsA total of four patients were included in this report. Mean follow-up time was 31 months, and all patients showed decreased tumour volume and signs of fibrosis during follow-up. One patient remained stable in terms of visual acuity, two patients lost visual acuity and one patient improved and had a functional visual acuity at last follow-up. One patient developed radiation retinopathy with subsequent neovascular glaucoma that needed further management. All other patients did not show any signs of radiation induced side effects.ConclusionWe report on the outcome of robotic CyberKnife radiosurgery in the treatment of uveal metastasis. We believe that single session, outpatient treatment delivery that can be facilitated with CyberKnife radiosurgery offer some benefits for this particularly sick group of patients.

Stereotactic radiosurgery (SRS) is a well-established treatment modality for the management of uveal melanoma, achieving high tumor control and eye retention rates. There are several SRS treatment platforms available, including the recently developed self-shielding gyroscopic radiosurgery (GRS) system. We report the first use of GRS in the treatment of uveal melanoma. We report the treatment of a 63-year-old female patient with a left-sided uveal melanoma. Akinesia of the ocular globe in the orbit was achieved by retrobulbar anesthesia. The treatment plan used six isocenters (three with the 10 mm and three with the 7.5 mm apertures) and 140 beams to cover 99.2% of the planning target volume (PTV) with 21 Gy at the 54% isodose line. Treatment was delivered in a single session with the GRS device. The total workflow time from retrobulbar anesthesia to completion of treatment was 122 minutes. The procedure was flawless, clinically well tolerated by the patient, and reliably performed in an outpatient setting, thus comparable to our published experience with robotic SRS. The evaluation of new radiosurgery treatment platforms is critical to maintaining quality standards and refining future treatments.

Background Is Gamma Knife surgery alone as effective as surgery plus whole brain irradiation (WBRT) for patients with a single, small-sized brain metastasis? Methods Patients aged between 18 and 80 years harboring a single, resectable metastasis ≤3 cm in diameter, a Karnofsky performance score (KPS) ≥70, and a stable systemic disease were randomly assigned to microsurgery plus WBRT or Gamma Knife surgery alone. The primary end point was length of survival, secondary end points were recurrence of tumor in the brain, health related quality of life, and treatment related toxicity. Results Due to poor patient accrual, the study was stopped prematurely. The final analysis was based on 33 patients in the surgery and 31 patients in the radiosurgery group. Treatment results did not differ in terms of survival ( P  = 0.8), neurological death rates ( P  = 0.3), and freedom from local recurrence ( P  = 0.06). Patients of the radiosurgery group experienced more often distant recurrences ( P  = 0.04); after adjustment for the effects of salvage radiosurgery this difference was lost ( P  = 0.4). Radiosurgery was associated with a shorter hospital stay, less frequent and shorter timed steroid application ( P  ≤ 0.001), and lower frequency of grade 1/2 toxicities (according to the RTOG/EORTC CNS toxicity criteria, P  ≤ 0.01). Improved scores for role functioning and quality of life were seen 6 weeks after radiosurgery ( P  < 0.05); this difference was lost 6 months after treatment. Conclusions In patients harboring a single, small-sized metastasis, Gamma Knife surgery alone is less invasive; local tumor control seems to be as high as after surgery plus WBRT. Distant tumor control, however, is significantly less frequently achieved (after radiosurgery alone). The role of radiosurgical salvage therapy (alternatively to WBRT) for distant tumor control deserves further prospective evaluation.

Objectives Radiosurgery (RS) using high-dose hypo-fractionated radiation is a novel treatment for renal cell carcinoma. This study investigates long-term oncological outcomes of RS for upper tract urothelial carcinoma (UTUC) in patients unfit for surgery or with a solitary kidney. Methods We performed a retrospective analysis of three prospective institutional databases from tertiary referral centers, including patients with UTUC treated with RS between 2008 and 2024. Results The study included 45 patients with a median age of 71.9 years (range 47.8–89.1). Of these, 28 had high-grade disease, and 9 carcinoma in situ (CIS). Twenty-eight patients had a solitary kidney. The median RS dose per fraction was 25 Gy (range 10–25). The median number of fractions was 1 (range 1–4 fractions). The median follow-up was 27.6 months (range 3.1–150.3), and the median overall survival (OS) was 91.7 months (95% CI 72.0–111.5). OS did not correlate with tumor grade or CIS. The median OS for low-grade patients was 52.06 months, while for high-grade patients, it was 87.90 months. Treatment response included complete response in 37 patients (82.2%), partial response in 2 (4.4%), stable disease in 2 (4.4%), and progression in 2 (4.4%). The median baseline and follow-up CKD-EPI were 64.2 and 53.5 mL/min/1.73 m2, respectively. Three patients (6.7%) required hemodialysis. Conclusions RS for UTUC is an effective local ablation therapy with durable long-term control and should be considered in patients not suitable for surgical approaches. It should be evaluated as a potential new standard of care in prospective studies in conjunction with peri-interventional systemic therapy.

To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma. Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3-10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years. Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery.