Adapting to change: exploring perceptions and demands of the coronavirus (COVID-19) workforce changes - an Australian multi-institutional radiation oncology survey.

Objective To evaluate the perceptions of the coronavirus disease 2019 (COVID-19) initiated workplace strategies implemented in radiation oncology departments across Australia. Methods A multidisciplinary team from Princess Alexandra Hospital developed a survey to address the impact of the pandemic strategies on areas such as patient care, staff education, well-being, flexible working arrangements, and research. The survey was conducted from November 2020 to April 2021. Results Out of 210 respondents from seven institutions, 45% reported burnout and 57% experienced work work-related stress. A significant majority of respondents were in favour of continued remote work (86%, 131/153). Radiation oncologists identified administrative or non-clinical work (92%, 34/37), telehealth clinics (32%, 12/37), or radiation therapy planning (22%, 8/37) as suitable for remote work. Additionally, 54% (21/39) of the radiation oncologists plan to use telehealth more frequently, with 67% (26/39) feeling more confident with the technology. The majority (81%, 171/210) of participants favoured continuation of hybrid in-person and virtual meetings. Virtual solutions were adopted for quality assurance activities (72%, 118/165) and 52% (60/116) indicated preference for ongoing utility of virtual platforms. However, 38% (79/210) of the respondents expressed concerns about the negative impact on junior staff training. Conclusion These findings reveal a strong inclination towards technological advancements and remote work arrangements to enable flexible working conditions. Our study suggests the need for ongoing reforms, focusing on improving clinical service delivery efficiencies and enhancing job satisfaction among clinicians.

Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.

Management and outcomes of glioblastoma: 20-year experience in a single Australian institution.

INTRODUCTION: We aimed to evaluate the changing patterns in the management of glioblastoma (GBM) and impact on survival outcomes over a 20-year period. METHODS: This is a retrospective study of patients diagnosed with GBM between 2001 and 2020, who had radiation therapy (RT) in an Australian institution. The primary outcomes were changes in treatment modalities (including surgery, RT, and chemotherapy) over time and overall survival (OS). Multivariable Cox regressions were used to evaluate factors associated with OS, including age, sex, ECOG performance status, treatment modalities, treatment facility, and year of treatment. RESULTS: 1079 patients were included in this study. Thirty-five per cent of patients had gross total resection, increasing from 31% in 2001-2005 to 45% in 2016-2020 (P < 0.001). Sixty-four per cent of patients had ≥60 Gy RT, increasing from 57% in 2001-2005 to 66% in 2016-2020 (P < 0.001). Seventy-five per cent of patients had chemotherapy, increasing from 22% in 2001-2005 to 89% in 2016-2020 (P < 0.001). Treatment received varied based on patients' age and ECOG performance status. The median OS for the entire cohort was 13.0 months (95% CI = 12.0-13.7). Median OS in patients who had maximal treatment (i.e., gross total resection, ≥60 Gy RT and chemotherapy) was 20.6 months (95% CI = 17.3-22.8). In multivariable analyses, age, sex, treatment facility, extent of surgical resection, RT dose, and chemotherapy use were associated with OS. CONCLUSION: This is one of the largest Australian series on the management and outcomes of GBM spanning a 20-year period. We observed improvement in OS over time, which is likely associated with evolving treatment options over the study period.

Dodecafluoropentane Emulsion as a Radiosensitizer in Glioblastoma Multiforme.

Purpose: Glioblastoma multiforme (GBM) is a hypoxic tumor resistant to radiotherapy. The purpose of this study was to assess the safety and efficacy of a novel oxygen therapeutic, dodecafluoropentane emulsion (DDFPe), in chemoradiation treatment of GBM. Experimental Design: In this multicenter phase Ib/II dose-escalation study, patients were administered DDFPe via intravenous infusion (0.05, 0.10, or 0.17 mL/kg) while breathing supplemental oxygen prior to each 2 Gy fraction of radiotherapy (30 fractions over 6 weeks). Patients also received standard-of-care chemotherapy [temozolomide (TMZ)]. Serial MRI scans were taken to monitor disease response. Adverse events were recorded and graded. TOLD (tissue oxygenation level-dependent) contrast MRI was obtained to validate modulation of tumor hypoxia. Results: Eleven patients were enrolled. DDFPe combined with radiotherapy and TMZ was well tolerated in most patients. Two patients developed delayed grade 3 radiation necrosis during dose escalation, one each at 0.1 and 0.17 mL/kg of DDFPe. Subsequent patients were treated at the 0.1 mL/kg dose level. Kaplan-Meier analysis showed a median overall survival of 19.4 months and a median progression-free survival of 9.6 months, which compares favorably to historical controls. Among 6 patients evaluable for TOLD MRI, a statistically significant reduction in tumor T1 was observed after DDFPe treatment. Conclusions: This trial, although small, showed that the use of DDFPe as a radiosensitizer in patients with GBM was generally safe and may provide a survival benefit. This is also the first time than TOLD MRI has shown reversal of tumor hypoxia in a clinical trial in patients. The recommended dose for phase II evaluation is 0.1 mL/kg DDFPe.Trial Registration: NCT02189109. Significance: This study shows that DDFPe can be safely administered to patients, and it is the first-in-human study to show reversal of hypoxia in GBM as measured by TOLD MRI. This strategy is being used in a larger phase II/III trial which will hopefully show a survival benefit by adding DDFPe during the course of fractionated radiation and concurrent chemotherapy.

Real-world data on patterns and outcomes of radiation therapy for brain metastases in a population-based cohort of lung cancer patients in Victoria.

INTRODUCTION: We evaluated real-world data on the patterns and outcomes of radiotherapy (RT) for brain metastases (BM) in a population-based cohort of patients with lung cancer (LC) in Victoria. METHODS: The Victorian Radiotherapy Minimum Data set (VRMDS) and the Victorian Cancer Registry (VCR) were linked to identify patients with LC who underwent RT for BM between 2013 and 2016. We determined: (i) proportion of patients treated with stereotactic radiosurgery (SRS); (ii) overall survival (OS); and (iii) 30-day mortality (30M) following RT for BM. RESULTS: Of the 1001 patients included in the study, 193 (19%) had SRS. There was no significant increase in SRS use over time - from 18% in 2013 to 21% in 2016 (P-trend = 0.8). In multivariate analyses, increased age (P = 0.03) and treatment in regional centres (P < 0.001) were independently associated with lower likelihood of SRS treatment. The median OS following RT for BM was 3.6 months. Patients who had SRS had better OS than those who did not have SRS (median OS 8.9 months vs. 3 months, P < 0.01). SRS use, age, sex and year of treatment were independently associated with OS in multivariate analyses. A total of 184 (18%) patients died within 30 days of RT for BM, and the proportion was higher in older (P = 0.001) and male patients (P = 0.004). CONCLUSION: One-in-five LC patients who received RT for BM had SRS. The improved OS with SRS is likely confounded by patient selection. It is important to reduce 30M by better selecting patients who may not benefit from RT for BM.

Oesophageal IGRT considerations for SBRT of LA-NSCLC: barium-enhanced CBCT and interfraction motion.

BACKGROUND: To determine the optimal volume of barium for oesophageal localisation on cone-beam CT (CBCT) for locally-advanced non-small cell lung cancers (NSCLC) and quantify the interfraction oesophageal movement relative to tumour. METHODS: Twenty NSCLC patients with mediastinal and/or hilar disease receiving radical radiotherapy were recruited. The first five patients received 25 ml of barium prior to their planning CT and alternate CBCTs during treatment. Subsequent five patient cohorts, received 15 ml, 10 ml and 5 ml. Six observers contoured the oesophagus on each of the 107 datasets and consensus contours were created. Overall 642 observer contours were generated and interobserver contouring reproducibility was assessed. The kappa statistic, dice coefficient and Hausdorff Distance (HD) were used to compare barium-enhanced CBCTs and non-enhanced CBCTs. Oesophageal displacement was assessed using the HD between consensus contours of barium-enhanced CBCTs and planning CTs. RESULTS: Interobserver contouring reproducibility was significantly improved in barium-enhanced CBCTs compared to non-contrast CBCTs with minimal difference between barium dose levels. Only 10 mL produced a significantly higher kappa (0.814, p = 0.008) and dice (0.895, p = 0.001). The poorer the reproducibility without barium, the greater the improvement barium provided. The median interfraction HD between consensus contours was 4 mm, with 95% of the oesophageal displacement within 15 mm. CONCLUSIONS: 10 mL of barium significantly improves oesophageal localisation on CBCT with minimal image artifact. The oesophagus moves substantially and unpredictably over a course of treatment, requiring close daily monitoring in the context of hypofractionation.

Temporal determinants of tumour response to neoadjuvant rectal radiotherapy.

INTRODUCTION: In locally advanced rectal cancer, longer delay to surgery after neoadjuvant radiotherapy increases the likelihood of histopathological tumour response. Chronomodulated radiotherapy in rectal cancer has recently been reported as a factor increasing tumour response to neoadjuvant treatment in patients having earlier surgery, with patients receiving a larger proportion of afternoon treatments showing improved response. This paper aims to replicate this work by exploring the impact of these two temporal factors, independently and in combination, on histopathological tumour response in rectal cancer patients. METHODS: A retrospective review of all patients with rectal adenocarcinoma who received long course (≥24 fractions) neoadjuvant radiotherapy with or without chemotherapy at a tertiary referral centre was conducted. Delay to surgery and radiotherapy treatment time were correlated to clinicopathologic characteristics with a particular focus on tumour regression grade. A review of the literature and meta-analysis were also conducted to ascertain the impact of time to surgery from preoperative radiotherapy on tumour regression. RESULTS: From a cohort of 367 patients, 197 patients met the inclusion criteria. Complete pathologic response (AJCC regression grade 0) was seen in 46 (23%) patients with a further 44 patients (22%) having at most small groups of residual cells (AJCC regression grade 1). Median time to surgery was 63 days, and no statistically significant difference was seen in tumour regression between patients having early or late surgery. There was a non-significant trend towards a larger proportion of morning treatments in patients with grade 0 or 1 regression (p = 0.077). There was no difference in tumour regression when composite groups of the two temporal variables were analysed. Visualisation of data from 39 reviewed papers (describing 27379 patients) demonstrated a plateau of response to neoadjuvant radiotherapy after approximately 60 days, and a meta-analysis found improved complete pathologic response in patients having later surgery. CONCLUSIONS: There was no observed benefit of chronomodulated radiotherapy in our cohort of rectal cancer patients. Review of the literature and meta-analysis confirms the benefit of delayed surgery, with a plateau in complete response rates at approximately 60-days between completion of radiotherapy and surgery. In our cohort, time to surgery for the majority of our patients lay along this plateau and this may be a more dominant factor in determining response to neoadjuvant therapy, obscuring any effects of chronomodulation on tumour response. We would recommend surgery be performed between 8 and 11 weeks after completion of neoadjuvant radiotherapy in patients with locally advanced rectal cancer.

Stereotactic Radiation Therapy Combined With Immunotherapy Against Metastatic Melanoma: Long-Term Results of a Phase 1 Clinical Trial.

PURPOSE: To determine the maximum tolerated dose (MTD) of stereotactic ablative radiation therapy (SABR) in combination with immunotherapy for the treatment of patients with metastatic melanoma. The study also investigates the effects of timing and dosing of SABR on clinical efficacy. METHODS: Metastatic melanoma patients with at least 2 metastases received SABR to a single metastatic site. All patients had standard dose immunotherapy with anti-PD1 or anti-CTLA4 at the discretion of their treating clinician. Following a standard 3 + 3 design, patients were escalated through 3 SABR doses (10 Gy, 15 Gy, and 20 Gy) delivered at 3 different time points (with cycle 1, 2, or 3 of immunotherapy). Dose-limiting toxicities (DLT) were defined as grade 3 or higher toxicity within 3 months of first treatment and assessed by an independent data safety monitoring committee (IDSMC). Logistic or Cox regressions were used to assess the impact of SABR dose and timing on the progression free (PFS) and overall survival (OS) of this cohort. RESULTS: Twenty-four patients were enrolled with a median clinical follow-up of 28 months. Four patients (16.7%) developed DLTs; 1 DLT occurred at a SABR-treated site, and all patients received 15 Gy. On this basis the IDSMC recommended stopping the trial and the MTD was defined at 10 Gy. The 2-year PFS was 21.9% (95% CI, 7.1%-41.8%) and 2-year OS was 49.6% (95% CI, 28.7%-67.6%). The median PFS for those receiving 10 Gy was numerically higher than for those receiving 15 Gy, 8.3 months versus 2.1 months (P = .38). The only treatment-related factor associated with both improved PFS (HR 0.08, P < .01) and OS (HR 0.008, P ≤ .01) was receiving SABR with cycle 3. SABR dose (PFS P = .17, OS P = .50) was not significant. CONCLUSIONS: SABR at 10 Gy can be safely combined with immunotherapy. SABR timing appears to influence efficacy more than dose and warrants consideration in research attempting to optimize synergism.

Long-term treatment outcomes of patients with primary optic nerve sheath meningioma treated with stereotactic radiotherapy.

We analysed the long-term outcomes of patients with primary optic nerve sheath meningioma (ONSM) treated with stereotactic radiotherapy (SRT). 26 patients with primary ONSM were treated with SRT between 2004 and 2013 at a single institution. SRT was delivered with image guidance to a median dose of 50.4 Gy in 28 fractions. 4 patients had prior surgical debulking. At a median radiological follow-up of 68 months, the MRI based tumour control was 100%. Visual acuity improved in 10 (38.4%), remained stable in 10 (38.4%) and was reduced in 6 (23.1%) patients following treatment. Stable or improved vision post-treatment was seen in 92.3% of patients with good pre-treatment vision (best corrected visual acuity 6/18 or better), compared to only 61.5% of patients with poor pre-treatment vision (best corrected visual acuity 6/24 or worse). Overall, the treatment was well tolerated with no Grade 2 or greater acute toxicity. Minimal other ophthalmic complications were seen with only one patient developing late onset Grade 3 radiation retinopathy.

Contemporary practice patterns of stereotactic radiosurgery for brain metastasis: A review of published Australian literature.

There has been a shift in the management of brain metastasis (BM), with increasing use of stereotactic radiosurgery (SRS) and delaying/avoiding whole-brain radiotherapy (WBRT), given the concern regarding the long-term neurocognitive effect and quality of life impact of WBRT. It is, however, unclear as to the contemporary practice pattern and outcomes of SRS in Australia. We conducted a literature search in PubMed and MEDLINE using a series of keywords: 'stereotactic', 'radiosurgery' and 'brain metastases', limiting to Australian studies, which report on clinical outcomes following SRS. Eight studies - one randomized trial and seven retrospective cohort studies - were identified and included in this review. A total of 856 patients were included, with the most common primary tumour types being melanoma, lung cancer and breast cancer. Approximately half of the patients had solitary BM, while 7% had 10 or more BM lesions. SRS is not routinely given in combination with WBRT. The 6-month intracranial control and 1-year intracranial control following SRS were reported in the range of 67-87% and 48-82%, respectively, whereas the 1-year overall survival and 2-year overall survival were reported in the range of 37-60% and 20-36%, respectively. There are limited data reported on SRS-related toxicities in all included studies. Overall, despite increasing use of SRS for BM, there is a low number of published Australian series in the literature. There is a potential role for establishing an Australian clinical quality registry or collaborative consortium for SRS in BM, to allow for systematic prospective data collection, and benchmarking of quality and outcomes of SRS.

Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial.

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).

Fractionated Stereotactic Radiotherapy for Cavernous Venous Malformations of the Orbital Apex.

PURPOSE: The objective of this study was to investigate the efficacy and safety of fractionated stereotactic radiotherapy in the treatment of cavernous venous malformation of the orbital apex. METHODS: The authors reviewed a prospective database from a single center of patients with cavernous venous malformation of the orbital apex who had treatment with fractionated stereotactic radiotherapy. The authors compared the symptoms, visual function and the size of the tumor pre- and posttreatment as well as reviewed the treatment details and the incidence of complications. RESULTS: Six patients received treatment with fractionated stereotactic radiotherapy for cavernous venous malformation involving the orbital apex. The median age was 48 (range, 32-63), and 50% were female. Patients received a dose of 45 to 50.4 Gy in 1.8 to 2 Gy fractions. Median follow up was 33 months (range, 18-66 months). The average tumor volume reduction at posttreatment imaging after 12 months was 63%. All lesions reduced in size postradiotherapy and remained controlled for the duration of follow up. All patients who had proptosis or a visual field defect had an improvement in the symptoms posttreatment. There were no complications of the treatment. CONCLUSION: Fractionated stereotactic radiotherapy appears to be a safe and effective management option for cavernous venous malformation of the orbital apex and leads to a sustained reduction of the volume of the lesion with associated improvement in symptoms and visual function.

Contrast enhanced oesophageal avoidance for stereotactic body radiotherapy: Barium vs. Gastrografin.

INTRODUCTION: SABR may facilitate treatment in a greater proportion of locally-advanced NSCLC patients, just as it has for early-stage disease. The oesophagus is one of the key dose-limiting organs and visualization during IGRT would better ensure toxicity is avoided. As the oesophagus is poorly seen on CBCT, we assessed the extent to which this is improved using two oral contrast agents. MATERIALS & METHODS: Six patients receiving radiotherapy for Stage I-III NSCLC were assigned to receive 50 mL Gastrografin or 50 mL barium sulphate prior to simulation and pre-treatment CBCTs. Three additional patients who did not receive contrast were included as a control group. Oesophageal visibility was determined by assessing concordance between six experienced observers in contouring the organ. 36 datasets and 216 contours were analysed. A STAPLE contour was created and compared to each individual contour. Descriptive statistics were used and a Kappa statistic, Dice Coefficient and Hausdorff distance were calculated and compared using a t-test. Contrast-induced artefact was assessed by observer scoring. RESULTS: Both contrast agents significantly improved the consistency of oesophagus localisation on CBCT across all comparison metrics compared to CBCTs without contrast. Barium performed significantly better than Gastrografin with improved kappa statistics (p = 0.007), dice coefficients (p < 0.001) and Hausdorff distances (p = 0.002), although at a cost of increased image artefact. DISCUSSION: Barium produced lower delineation uncertainties but more image artefact, compared to Gastrografin and no contrast. It is feasible to use oral contrast as a tool in IGRT to help guide clinicians and therapists with online matching and monitoring of the oesophageal position.

TROG 15.03 phase II clinical trial of Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney - FASTRACK II.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.

Long-term survivors of glioblastoma: a closer look.

Glioblastoma has a poor prognosis with median survival of 12-14 months. Long-term survivors (LTS), alive at least 2 years from diagnosis, comprise 13% of this population. This study aims to provide a clinical profile of LTS at two institutions in Melbourne, Australia. Histological diagnosis of glioblastoma from 1st January 2006 to 31st December 2012 were identified from pathology/oncology databases. Demographic, treatment and survival characteristics were recorded (follow-up to 31st December 2015). Relevant inter-group statistics were used to identify differences between LTS and those surviving less than 2 years. Survival estimated by Kaplan-Meier. 776 patients were identified with 154 surviving > 2 years. Compared with patients surviving < 2 years, LTS were more likely to be younger (median age 56 vs. 65 years, p < .001), have ECOG 0-2 (97 vs. 65%, p < .001), gross tumour resection (91 vs. 61%, p < .001), and receive chemoradiotherapy (94 vs. 40%, p < .001). Most common presenting symptoms amongst LTS were headache (42%), seizure (28%) and speech disturbance (16%). Of LTS, 111 patients (72%) progressed at a median of 20.1 months from diagnosis, with 46% undergoing a second craniotomy. The most common non-surgical second line treatments were temozolomide (41%), followed by radiotherapy (12%). One-third of LTS received three or more lines of treatment, and 10% underwent three or more craniotomies. LTS of glioblastoma (20%) are more likely to be younger, have unilateral tumours, good performance status and undergo multimodality treatment. These data may assist in predicting LTS at diagnosis and understanding their clinical journey to facilitate planning of treatment and supportive care.

Lung cancer radiation therapy in Australia and New Zealand: Patterns of practice.

INTRODUCTION: The RANZCR Faculty of Radiation Oncology Lung Interest Cooperative (FROLIC) surveyed patterns of lung cancer radiation therapy practice for non-small cell (NSCLC) and small cell lung cancer (SCLC) to evaluate current patterns of care and potential for improvement. METHODS: In October 2014, Radiation Oncologists (ROs) from all 62 departments in Australia and New Zealand were invited to a web-based survey directed at those treating lung cancer. Questions covered current radiation therapy practice as well as quality measures. RESULTS: Fifty-eight per cent of respondents used 4D-CT simulation. For curative treatment, 98% employed 3D-CRT and 34% intensity modulated radiotherapy (IMRT) techniques. Treatment verification was primarily performed using cone-beam CT (86%). In NSCLC, the commonest curative dose-fractionation regime was 60 Gy/30# (96%) and for palliative intent, 30 Gy/10# (76%). Forty-four per cent treated patients with stereotactic ablative body radiotherapy (SABR) and half treated central tumours with this technique. In fit patients with synchronous solitary brain metastases, 80% would give radical treatment. For curative-intent SCLC, 45-50.4 Gy/25-28# (61%) and 45 Gy/30#/1.5 Gy b.d. (48%) were used. Ninety-four per cent discussed lung cancer patients at multidisciplinary meetings. Contours were peer-reviewed by 74% and 50% for conventional fractionation and SABR respectively. CONCLUSION: A significant proportion of ROs did not have access to 4D-CT. The majority used 3D image verification and consistently prescribed evidence based doses. A significant number did not participate in peer-review of contours. Practice in IMRT and synchronous oligo-metastatic disease is variable and should be an area of future research. Utilising survey findings, FROLIC is developing consensus recommendations to guide practice.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

BACKGROUND: Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). METHODS: Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. RESULTS: IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. CONCLUSIONS: Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Multimodality guidance for accurate bronchoscopic insertion of fiducial markers.

INTRODUCTION: Fiducial markers act as visible surrogates of tumor position during image-guided radiotherapy. Marker placement has been attempted percutaneously but is associated with high rates of pneumothorax and chest drain placement. METHODS: Patients undergoing radical radiation treatment for non-small-cell lung cancer underwent bronchoscopic implantation of gold fiducials using radial probe endobronchial ultrasound (EBUS) with virtual bronchoscopy and fluoroscopic guidance to achieve tumor localization and placement within/adjacent to peripheral lung tumors. For tumors not localized using radial EBUS, fiducial placement was achieved by electromagnetic navigation to the vicinity of the tumor. RESULTS: Eighteen fiducials were placed to mark 16 lesions in 15 patients. In nine patients (60%), fiducials were implanted at the time of diagnostic bronchoscopy. No procedural complications occurred. EBUS localization allowed marker implantation within the target lesion in 12 cases. In four lesions, electromagnetic navigation bronchoscopy-guided implantation achieved a median fiducial-lesion distance of 6 mm (mean 12 mm). No marker migration occurred after the implantation of two-band markers; however, early migration was observed in two of eight (25%) of the smaller linear fiducials. No migration during the course of radiation therapy was observed. CONCLUSION: Fiducial marker placement is easily and safely performed bronchoscopically, including at the time of diagnostic bronchoscopy. Marker geometry appears important in stability of bronchoscopically inserted fiducials. Future studies are required to confirm the optimal marker size, geometry, and spatial relationship with the target lesion.