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The Canadian Cancer Trials Group (CCTG) Symptom Control 24 protocol (SC.24) was a multicenter randomized controlled phase 2/3 trial conducted in Canada and Australia. Patients with painful spinal metastases were randomized to either 24 Gy/2 stereotactic body radiation therapy (SBRT) or 20 Gy/5 conventional external beam radiation therapy (CRT). The study met its primary endpoint and demonstrated superior complete pain response rates at 3 months following SBRT (35%) versus CRT (14%). SBRT planning and delivery is resource intensive. Given its benefits in SC.24, we performed an economic analysis to determine the incremental cost-effectiveness of SBRT compared with CRT. The trial recruited 229 patients. Cost-effectiveness was assessed using a Markov model taking into account observed survival, treatments costs, retreatment, and quality of life over the lifetime of the patient. The EORTC-QLU-C10D was used to determine quality of life values. Transition probabilities for outcomes were from available patient data. Health system costs were from the Canadian health care perspective and were based on 2021 Canadian dollars (CAD). The incremental cost-effectiveness ratio (ICER) was expressed as the ratio of incremental cost to quality-adjusted life years (QALY). The impact of parameter uncertainty was investigated using deterministic and probabilistic sensitivity analyses. The base case for SBRT compared with CRT had an ICER of $9,040CAD per QALY gained. Sensitivity analyses demonstrated that the ICER was most sensitive to variations in the utility assigned to "No local failure" ($5,457CAD to $241,051CAD per QALY), adopting low and high estimates of utility and the cost of the SBRT (ICERs ranging from $7345-$123,361CAD per QALY). It was more robust to variations in assumptions around survival and response rate. SBRT is associated with higher upfront costs than CRT. The ICER shows that, within the Canadian health care system, SBRT with 2 fractions is likely to be more cost-effective than CRT. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: To evaluate the use of stereotactic body radiation therapy (SBRT) for spine metastases and the associated factors in Australia. Methods: The Victorian Radiotherapy Minimum Dataset, which captures all episodes of radiotherapy delivered in the state of Victoria, was accessed to evaluate the patterns and trends of SBRT for spine metastases. The primary outcome was SBRT use and associated factors. Results: There were 6244 patients who received 8861 courses of radiotherapy for spine metastases between 2012 and 2017. Of these, 277 (3%) courses were SBRT, which increased from 0.4% in 2012 to 5% in 2017 (P-trend < 0.001). There was a higher proportion of SBRT use in patients with prostate cancer (6%) and melanoma (4%) compared to other cancers (2–3%) (p < 0.001). Patients from the highest socioeconomic quintiles (5%) were more likely to be treated with SBRT compared to patients from the lowest socioeconomic quintiles (3%) (p < 0.001). There was a higher proportion of SBRT use in private radiotherapy centres (6%) compared to public radiotherapy centres (1%) (p < 0.001). No spine SBRT was delivered in regional centres. In multivariate analyses, the year of treatment, age, primary cancers and radiotherapy centres were independently associated with SBRT use. Conclusion: This is the first Australian population-based study quantifying the increasing use of spine SBRT; however, the overall use of spine SBRT remains low. We anticipate an ongoing increase in spine SBRT, as spine SBRT gradually becomes the standard-of-care treatment for painful spine metastases. [ABSTRACT FROM AUTHOR]

Primary transitional cell carcinoma of the ureter is a rare type of cancer with metastasis presented in approximately 25% at diagnosis. Due to its rarity and poor prognosis, the management of this neoplasm is still controversial, and the development of new therapies is of uttermost importance. Herein, we describe a case of a 54-year-old patient diagnosed with transitional cell carcinoma of the left ureter submitted to left nephroureterectomy (pT3N2M0) and methotrexate, vinblastine, doxorubicin, and cisplatin adjuvant chemotherapy. A single liver metastasis was detected and combination chemotherapy with gemcitabine and carboplatin was initiated along with stereotactic body radiation therapy. Despite these 2 previous chemotherapy regimens, the patient presented disease progression and transarterial selective internal radiation therapy (SIRT) with yttrium-90 was indicated. This locoregional treatment was performed with the administration of 1.2 GBq yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, NSW, Australia) into the right hepatic artery. Another systemic treatment was immunotherapy using nivolumab with excellent tolerability. After 10 years of follow-up, at the last clinical evaluation, the patient had no clinical symptoms and the last imaging follow-up using positron emission tomography-computed tomography scan showed complete response. This report introduces upper urinary tract urothelial carcinoma as a distinct type of malignancy in which SIRT can be safely implemented. As a transition method to nivolumab, it was successful. There might be a potential therapeutic synergism between these 2 treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Conventional external beam radiotherapy is the standard palliative treatment for spinal metastases; however, complete response rates for pain are as low as 10-20%. Stereotactic body radiotherapy delivers high-dose, ablative radiotherapy. We aimed to compare complete response rates for pain after stereotactic body radiotherapy or conventional external beam radiotherapy in patients with painful spinal metastasis.Methods: This open-label, multicentre, randomised, controlled, phase 2/3 trial was done at 13 hospitals in Canada and five hospitals in Australia. Patients were eligible if they were aged 18 years and older, and had painful (defined as ≥2 points with the Brief Pain Inventory) MRI-confirmed spinal metastasis, no more than three consecutive vertebral segments to be included in the treatment volume, an Eastern Cooperative Oncology Group performance status of 0-2, a Spinal Instability Neoplasia Score of less than 12, and no neurologically symptomatic spinal cord or cauda equina compression. Patients were randomly assigned (1:1) with a web-based, computer-generated allocation sequence to receive either stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions or conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions using standard techniques. Treatment assignment was done centrally by use of a minimisation method to achieve balance for the stratification factors of radiosensitivity, the presence or absence of mass-type tumour (extraosseous or epidural disease extension, or both) on imaging, and centre. The primary endpoint was the proportion of patients with a complete response for pain at 3 months after radiotherapy. The primary endpoint was analysed in the intention-to-treat population and all safety and quality assurance analyses were done in the as-treated population (ie, all patients who received at least one fraction of radiotherapy). The trial is registered with ClinicalTrials.gov, NCT02512965.Findings: Between Jan 4, 2016, and Sept 27, 2019, 229 patients were enrolled and randomly assigned to receive conventional external beam radiotherapy (n=115) or stereotactic body radiotherapy (n=114). All 229 patients were included in the intention-to-treat analysis. The median follow-up was 6·7 months (IQR 6·3-6·9). At 3 months, 40 (35%) of 114 patients in the stereotactic body radiotherapy group, and 16 (14%) of 115 patients in the conventional external beam radiotherapy group had a complete response for pain (risk ratio 1·33, 95% CI 1·14-1·55; p=0·0002). This significant difference was maintained in multivariable-adjusted analyses (odds ratio 3·47, 95% CI 1·77-6·80; p=0·0003). The most common grade 3-4 adverse event was grade 3 pain (five [4%] of 115 patients in the conventional external beam radiotherapy group vs five (5%) of 110 patients in the stereotactic body radiotherapy group). No treatment-related deaths were observed.Interpretation: Stereotactic body radiotherapy at a dose of 24 Gy in two daily fractions was superior to conventional external beam radiotherapy at a dose of 20 Gy in five daily fractions in improving the complete response rate for pain. These results suggest that use of conformal, image-guided, stereotactically dose-escalated radiotherapy is appropriate in the palliative setting for symptom control for selected patients with painful spinal metastases, and an increased awareness of the need for specialised and multidisciplinary involvement in the delivery of end-of-life care is needed.Funding: Canadian Cancer Society and the Australian National Health and Medical Research Council. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions.Methods: This was a multi-institutional retrospective study of patients treated with SBRT for HCC at 10 institutions between January 2013 and December 2019. Patients' demographics, disease characteristics and SBRT details were evaluated.Results: Three hundred and seventeen patients were evaluated with a median age of 67 years (range, 32-90). Liver cirrhosis was present in 88.6%, baseline Child-Pugh score was A5/6 in 85.1% and B7/8 in 13.2%. Median size of HCC treated was 30 mm (range, 10-280). 63.1% had early-stage disease (Barcelona clinic liver cancer (BCLC) stage 0/A) and 36% had intermediate/advanced-stage disease (BCLC B/C). In 2013/2014, six courses of SBRT were delivered, increasing to 108 in 2019. SBRT was prescribed in five fractions for 71.3% of the cohort. The most common dose fractionation schedule was 40 Gy in five fractions (24.3%). Median biologically effective dose (BED10 ) delivered was 85.5 Gy for early-stage and 60 Gy for intermediate/advanced disease, respectively. The most common prescription range was 100-120 Gy BED10 (32.8%).Conclusion: SBRT utilisation for HCC is increasing in Australia. There was wide variation in size of tumours and disease stages treated, and prescription patterns. Uniform reporting of clinical and dosimetric details are important in refining the role of liver SBRT. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic ablative radiotherapy (SABR) for lung cancer is a modality of treatment that has improved outcomes for lung cancer patients. However, radiotherapy for lung cancer is underutilized and fewer than half of elderly patients with non‐small cell lung cancer (NSCLC) receive active treatment. The purpose of this study is to report on a collaboration in implementing an NSCLC SABR (stereotactic ablative body radiation) program safely, efficiently, and uniformly across several centers, including regional sites. The first aim of this paper is to detail the collaboration and implementation that started in 2013 and is ongoing. The second aim of this paper is to document early toxicities and quality of life outcomes. Method: A tripartite approach was used to develop the protocol and networks required for the implementation of SABR across multiple sites in NSW. Departments starting the programmes were supported and physics credentialing with central site submission was required before commencing the treatment. Additional ongoing support was available via an email discussion group involving all members of the collaboration. Results: Between July 22, 2013 and February 22, 2016, 41 patients were enrolled with 34 patients in active follow up. The toxicity profile so far is similar to those of published studies with no appreciable effect on quality of life outcomes. Conclusion: The collaboration formed an effective framework in facilitating the implementation of SABR across several sites in NSW and could be used as a model for the safe and uniform implementation of new technologies in Australia. [ABSTRACT FROM AUTHOR]

Highlights • Gamma Knife efficacy for treating greater numbers of brain metastases is unclear. • Survival outcomes in 180 cases with a median 5.5 (range 1–47) lesions were examined. • Total tumor volume was more effective in predicting outcome than tumor number. • Cases with volumes >9.1 cm3 had the poorest median survival time of 5.2 months. • A tumor volume index is encouraged for predicting stereotactic treatment outcomes. Abstract Background and purpose To assess the response of the first cohort of patients treated with Gamma Knife radiosurgery in Australia. Materials and methods A prospectively collected cohort of 180 patients with intracranial metastases from different primaries was treated between August 2010 and July 2017. Survival was calculated using the Kaplan–Meier's method. Cox regression was used for multivariate analysis. Results Currently 141 patients (78.3%) have died of their disease. The median survival for the group as a whole was 9.2 months, with observed differences resulting from the volume of tumor burden (11.4 months for volumes <3.2 cm3 to 5.16 months for volume >9.1 cm3). Overall 2-year survival was 20.7%. Conclusion Results from the first Gamma Knife radiosurgery center in Australia showed that the treatment is feasible and effective, consistent with the international experience. For patients with larger numbers of intracranial metastases, the total volume of the intracranial burden may be of more significance in predicting outcomes. While there appeared to be a difference in survival by histologic origin, this could be related to concurrent systemic immunotherapy available for certain tumors. [ABSTRACT FROM AUTHOR]

Background: Stereotactic ablative body radiotherapy (SABR) is widely used to treat inoperable stage 1 non-small-cell lung cancer (NSCLC), despite the absence of prospective evidence that this type of treatment improves local control or prolongs overall survival compared with standard radiotherapy. We aimed to compare the two treatment techniques.Methods: We did this multicentre, phase 3, randomised, controlled trial in 11 hospitals in Australia and three hospitals in New Zealand. Patients were eligible if they were aged 18 years or older, had biopsy-confirmed stage 1 (T1-T2aN0M0) NSCLC diagnosed on the basis of 18F-fluorodeoxyglucose PET, and were medically inoperable or had refused surgery. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and the tumour had to be peripherally located. Patients were randomly assigned after stratification for T stage and operability in a 2:1 ratio to SABR (54 Gy in three 18 Gy fractions, or 48 Gy in four 12 Gy fractions if the tumour was <2 cm from the chest wall) or standard radiotherapy (66 Gy in 33 daily 2 Gy fractions or 50 Gy in 20 daily 2·5 Gy fractions, depending on institutional preference) using minimisation, so no sequence was pre-generated. Clinicians, patients, and data managers had no previous knowledge of the treatment group to which patients would be assigned; however, the treatment assignment was subsequently open label (because of the nature of the interventions). The primary endpoint was time to local treatment failure (assessed according to Response Evaluation Criteria in Solid Tumors version 1.0), with the hypothesis that SABR would result in superior local control compared with standard radiotherapy. All efficacy analyses were based on the intention-to-treat analysis. Safety analyses were done on a per-protocol basis, according to treatment that the patients actually received. The trial is registered with ClinicalTrials.gov (NCT01014130) and the Australia and New Zealand Clinical Trials Registry (ACTRN12610000479000). The trial is closed to new participants.Findings: Between Dec 31, 2009, and June 22, 2015, 101 eligible patients were enrolled and randomly assigned to receive SABR (n=66) or standard radiotherapy (n=35). Five (7·6%) patients in the SABR group and two (6·5%) in the standard radiotherapy group did not receive treatment, and a further four in each group withdrew before study end. As of data cutoff (July 31, 2017), median follow-up for local treatment failure was 2·1 years (IQR 1·2-3·6) for patients randomly assigned to standard radiotherapy and 2·6 years (IQR 1·6-3·6) for patients assigned to SABR. 20 (20%) of 101 patients had progressed locally: nine (14%) of 66 patients in the SABR group and 11 (31%) of 35 patients in the standard radiotherapy group, and freedom from local treatment failure was improved in the SABR group compared with the standard radiotherapy group (hazard ratio 0·32, 95% CI 0·13-0·77, p=0·0077). Median time to local treatment failure was not reached in either group. In patients treated with SABR, there was one grade 4 adverse event (dyspnoea) and seven grade 3 adverse events (two cough, one hypoxia, one lung infection, one weight loss, one dyspnoea, and one fatigue) related to treatment compared with two grade 3 events (chest pain) in the standard treatment group.Interpretation: In patients with inoperable peripherally located stage 1 NSCLC, compared with standard radiotherapy, SABR resulted in superior local control of the primary disease without an increase in major toxicity. The findings of this trial suggest that SABR should be the treatment of choice for this patient group.Funding: The Radiation and Optometry Section of the Australian Government Department of Health with the assistance of Cancer Australia, and the Cancer Society of New Zealand and the Cancer Research Trust New Zealand (formerly Genesis Oncology Trust). [ABSTRACT FROM AUTHOR]

Background: This paper describes the multi-institutional prospective phase II clinical trial, SPARK: Stereotactic Prostate Adaptive Radiotherapy utilizing Kilovoltage Intrafraction Monitoring (KIM). KIM is a real-time image guided radiotherapy technology being developed and clinically pioneered for prostate cancer treatment in Australia. It has potential for widespread use for target radiotherapy treatment of cancers of the pelvis, thorax and abdomen.Methods: In the SPARK trial we will measure the cancer targeting accuracy and patient outcomes for 48 prostate cancer patients who will be treated in five treatment sessions as opposed to the conventional 40 sessions. The reduced number of treatment sessions is enabled by the KIM's increased cancer targeting accuracy.Discussion: Real-time imaging in radiotherapy has the potential to decrease the time taken during cancer treatment and reduce the imaging dose required. With the imaging being acquired during the treatment, and the analysis being automated, there is potential for improved throughput. The SPARK trial will be conducted under the auspices of the Trans-Tasman Radiation Oncology Group (TROG).Trial Registration: This trial was registered on ClinicalTrials.gov on 09 March 2015. The identifier is: NCT02397317. [ABSTRACT FROM AUTHOR]