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Alex L Dubrava,1,2 Pan Su Pyae Kyaw,1,2 Joseph Newman,1,2 Jarrad Pringle,1,2 Justin Westhuyzen,3 Gina La Hera Fuentes,2 Thomas P Shakespeare,1,2 Renukadas Sakalkale,2,4 Noel J Aherne1– 3 1Department of Radiation Oncology, Mid North Coast Cancer Centre, Coffs Harbour, New South Wales, Australia; 2Coffs Harbour Rural Clinical School, University of New South Wales, Coffs Harbour Health Campus, Coffs Harbour, New South Wales, Australia; 3School of Health and Human Sciences, Southern Cross University, Coffs Harbour, New South Wales, Australia; 4Coffs Harbour Base Hospital Pathology, Coffs Harbour, New South Wales, AustraliaCorrespondence: Noel J Aherne, Department of Radiation Oncology, Mid North Coast Cancer Centre, Coffs Harbour Hospital, Coffs Harbour, New South Wales, 2450, Australia, Tel + 61 2 6656 5125, Fax +61 2 6656 5855, Email noel.aherne@health.nsw.gov.auPurpose: Triple negative breast cancer (TNBC) is a breast carcinoma subtype that neither expresses estrogen (ER) and progesterone receptors (PR) nor the human epidermal growth factor receptor 2 (HER2). Patients with TNBC have been shown to have poorer outcomes mainly owing to the limited treatment options available. However, some studies have shown TNBC tumors expressing androgen receptors (AR), raising hopes of its prognostic role.Patients and Methods: This retrospective study investigated the expression of AR in TNBC and its relationship with known patient demographics, tumor and survival characteristics. From the records of 205 TNBC patients, 36 had available archived tissue samples eligible for AR staining. For statistical purposes, tumors were classified as either “positive” or “negative” for AR expression. The nuclear expression of AR was scored by measuring the percentage of stained tumor cells and its staining intensity.Results: AR was expressed by 50% of the tissue samples in our TNBC cohort. The relationship between AR status with age at the time of TNBC diagnosis was statistically significant, with all AR positive TNBC patients being greater than 50 years old (vs 72.2% in AR negative TNBC). Also, the relationship between AR status and type of surgery received was statistically significant. There were no statistically significant associations between AR status with other tumor characteristics including “TNM status”, tumor grade or treatments received. There was no statistically significant difference in median survival between AR negative and AR positive TNBC patients (3.5 vs 3.1 years; p = 0.581). The relationship between OS time and AR status (p = 0.581), type of surgery (p = 0.061) and treatments (p = 0.917) were not statistically significant.Conclusion: The androgen receptor may be an important prognostic marker in TNBC, with further research warranted. This research may benefit future studies investigating receptor-targeted therapies in TNBC.Keywords: triple negative, breast cancer, androgen receptor

The discovery of tyrosine kinase oncogenic driver mutations, including anaplastic lymphoma kinase (ALK), has changed the face of non-small cell lung cancer (NSCLC) treatment. Whilst the development of tyrosine kinase inhibitors has improved survival, with their increasing use, it is important to be aware of the risks of rare yet serious adverse events, such as drug-induced pulmonary toxicity. Whilst little is known in regard to drug-induced pneumonitis in the setting of ALK inhibitors, such reactions carry a high morbidity and mortality rate, impacting greatly upon options for further treatment and management. We describe the case of a 73-year-old female with metastatic ALK-positive NSCLC who developed subacute dyspnoea 3 weeks after commencing lorlatinib. She was diagnosed with drug-induced pneumonitis, from which she recovered clinically following the cessation of her targeted therapy. Pneumonitis related to lorlatinib is a rare pulmonary toxicity, and early recognition and intervention is critical to reduce the associated risks of respiratory failure and death.

Introduction Evidence-based AustralianAQ5 guidelines (eviQ) recommend adjuvant supraclavicular fossa irradiation after axillary lymph node dissection (ALND) in node-positive breast cancer patients. Disparity between surgically determined versus computed tomography (CT) determined nodal volumes may result in discontiguous nodal volumes and untreated nodal tissue. We examine the extent of untreated nodal tissue in women with breast cancer post-level II or III ALND and adjuvant radiation therapy (RT) using ESTRO contouring guidelines. Methods Female breast cancer patients who underwent level II and III ALND with apical clip placement from 2016 to 2020 and CT simulated in supine position were included. CT-defined axillary level II-IV volumes were contoured using ESTRO guidelines. The distance between the apical clip and RT nodal volumes was measured to indicate extent of untreated tissue. Results Of 34 eligible patients treated by 7 surgeons, 76% had level II ALND and 24% level III ALND. Only 5.9% of clips entirely encompassed the corresponding RT nodal volumes. 55.9% of clips fell within and 44.1% fell inferolaterally outside the corresponding RT nodal volumes. A median 3.6 cm (range 0-7.5 cm) of undissected nodal tissue would not be included within standard RT target volumes following eviQ recommendations. Conclusion There is a disparity between surgically determined versus CT determined axillary nodal volumes, leading to discontiguous nodal volumes and untreated axillary nodal tissue, despite following standard radiation contouring guidelines. Intraoperatively placed apical axillary clips may assist radiation oncologists to accurately delineate undissected nodal tissues at risk.

Purpose The five grade group system has been validated for men treated with radical prostatectomy. However, the prognostic value for men treated with radiation therapy is uncertain, with prior studies utilising old techniques and doses. We aimed to validate the International Society of Urological Pathology (ISUP) groupings for men treated with contemporary radiation therapy. Methods Men with localised prostate cancer treated with image-guided, dose-escalated (≥78 Gy) external beam radiation were identified across four institutions. Primary outcome was time to biochemical failure. Harrell’s C index assessed performance of the ISUP system against other grading stratifications. Results 2205 men were included, with median follow-up of 5.6 years. Seven-year actuarial rates of biochemical failure for grade groups 1–5 were 9.3%, 10.4%, 13.2%, 12.4% and 23.4%. On multivariate analysis, hazard ratios for biochemical failure were 1.19, 1.00, 1.10, 1.05 and 2.10 for grade groups 1–5, relative to 2. P values were only significant for grade group 5. Harrell’s C index favoured an alternative three group model (comprising Gleason scores [6 and 3 + 4 = 7] vs [4 + 3 = 7 and 8] vs [9 and 10]) over ISUP grade groups. Conclusions The ISUP grade groups were not validated in a contemporary cohort treated with dose-escalated, image-guided radiation therapy. Grade groups 1–4 were not statistically different from each other; however, grade group 5 had a significantly worse prognosis. We identified a new three group model that better predicted biochemical outcomes. Further work is required to validate optimal groupings for modern radiation therapy and investigate the contrasting prognostic capability of grade groups in surgical and radiation therapy patients.

Machine learning technology has a growing impact on radiation oncology with an increasing presence in research and industry. The prevalence of diverse data including 3D imaging and the 3D radiation dose delivery presents potential for future automation and scope for treatment improvements for cancer patients. Harnessing this potential requires standardization of tools and data, and focused collaboration between fields of expertise. The rapid advancement of radiation oncology treatment technologies presents opportunities for machine learning integration with investments targeted towards data quality, data extraction, software, and engagement with clinical expertise. In this review, we provide an overview of machine learning concepts before reviewing advances in applying machine learning to radiation oncology and integrating these techniques into the radiation oncology workflows. Several key areas are outlined in the radiation oncology workflow where machine learning has been applied and where it can have a significant impact in terms of efficiency, consistency in treatment and overall treatment outcomes. This review highlights that machine learning has key early applications in radiation oncology due to the repetitive nature of many tasks that also currently have human review. Standardized data management of routinely collected imaging and radiation dose data are also highlighted as enabling engagement in research utilizing machine learning and the ability integrate these technologies into clinical workflow to benefit patients. Physicists need to be part of the conversation to facilitate this technical integration.

Androgen deprivation therapy (ADT) is a key component of therapy for patients with high-risk prostate carcinoma, but it may be deleterious for bone health. We sought to determine the frequency of dual energy x-ray absorptiometry (DXA) scanning in patients commencing adjuvant ADT for treatment of high-risk prostate cancer at a large integrated regional cancer centre.The electronic medical records (EMR) of all patients with high-risk prostate carcinoma commenced on adjuvant ADT between January 1, 2016 and December 31, 2017 at the Mid-North Coast Cancer Institute, Coffs Harbour, Australia were reviewed. Patients commenced on neoadjuvant ADT and long-term suppressive ADT for metastatic disease were excluded. The following data were obtained: socio-demographic information, prostate cancer data, ADT details and DXA results.188 men (mean age ± SD, 75.4 ± 7 years) were commenced on adjuvant ADT for a total duration (mean ± SD) of 23.4 ± 7 months. Most (n = 155/188, 82%) were commenced onA high level (85%) of DXA scanning in men commencing ADT for prostate cancer can be achieved at a regional centre. The high prevalence (72%) of low bone mass in our unselected cohort underscores the importance of routine DXA scanning to guide bone health management during ADT.

Background Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014–2018. Methods Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. Results There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014–2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. Conclusions Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

Introduction New techniques for adjuvant radiation therapy after breast conservation include prone positioning, hypofractionation and intensity-modulated radiation therapy (IMRT). Long-term evaluations of this combination are lacking, and we report our own experience. Methods Patients with invasive breast cancer followed for a minimum 36 months post-IMRT were eligible. Dose used was 40 Gray in 15 fractions over 3 weeks to the whole breast via forward-planned prone, whole breast IMRT. A 10 Gy in 5 fraction supine boost was offered. Results Between January 2012 and January 2020, 2199 patients had breast conservation and adjuvant radiation: 489 received hypofractionated prone breast IMRT, with 155 eligible for our evaluation. Median follow-up was 52 months. Median age was 62 (range 36-80), 78.7% were T1, 20.6% were T2, and 12.3% were node-positive. Grade was 1 in 26.5%, 2 in 43.9% and 3 in 29.7%; 87.1% were oestrogen receptor positive, 3.2% were HER2 positive, and 11.0% were triple negative. 58.6% received a boost, 74.8% endocrine therapy and 32.3% chemotherapy. No patient developed local recurrence. One regional recurrence was successfully salvaged. Six patients (3.9%) developed metastases, and 1.9% died. Five-year actuarial local recurrence-free, regional recurrence-free and breast cancer-specific survival rates were 100.0%, 98.2% and 94.8%. Late grade 1 and 2 breast pain occurred in 20.0% and 1.3% of patients. Only 11.0% had new pain compared to pre-radiation. No patient developed radiation-induced pneumonitis, pulmonary fibrosis, rib fracture or cardiac toxicity. All patients scored cosmesis as 'good' or better. Conclusion Adjuvant hypofractionated prone breast IMRT has excellent locoregional control and minimal toxicity.

Purpose Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases and is associated with a poor prognosis. In this retrospective study of patients undergoing radiation therapy as part of their treatment, disease-free survival (DFS) and overall survival (OS) of TNBC patients were examined in relation to clinical and treatment-related factors. Patients and methods The electronic records of 214 consecutive TNBC patients treated with surgery followed by radiotherapy at the Mid North Coast Cancer Institute between 2006 and 2016 were reviewed. Overall survival and DFS times were analyzed using the Kaplan-Meier method; multivariate Cox proportional hazard regression modelling was used to assess the significance of prognostic factors. Results The majority of tumors were T1 (51.9%), followed by T2 (39.2%) and T3 (6.1%). For the whole group, mean DFS was 106.4 (SD 48.7) months; OS 109.4 (SD 52.1) months. Radiotherapy technique, fractionation protocol and laterality were not significant factors for DFS or OS (p>0.05). However, compared to breast conservation, mastectomy was associated with poorer DFS (mean 114.2 vs 65.2 months; p Conclusion Advanced disease exhibited by tumor size > 5cm and positive nodal status is associated with poorer DFS in TNBC patients. Radiotherapy technique or fractionation protocol were not associated with differences in DFS or OS in our patient cohort.

To assess the prognostic value of the neutrophil-lymphocyte ratio (NLR) in a cohort of triple-negative breast cancer patients (TNBC) treated in a regional cancer center.The electronic medical records of 214 consecutive patients treated with surgery, chemotherapy, and radiotherapy between 2006 and 2016 were reviewed. The prognostic significance of the NLR for disease-free survival (DFS) and overall survival (OS) was examined in relation to clinical and treatment-related factors. Overall survival and DFS were assessed using the Kaplan-Meier method; Cox semi-parametric regression modelling was used for multivariate analysis.Ninety patients were eligible; median follow-up was 45.6 months (range, 6-105 months). The 3-year OS rate was 77.9% and the 5-year OS rate 61.7%. Patients with an NLR of ≤1.7 had significantly better DFS (While NLR is associated with survival in TNBC patients on univariate analysis, the prognostic value of NLR is likely due to its association with other clinicopathological factors.

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.

Introduction There is significant potential to analyse and model routinely collected data for radiotherapy patients to provide evidence to support clinical decisions, particularly where clinical trials evidence is limited or non-existent. However, in practice there are administrative, ethical, technical, logistical and legislative barriers to having coordinated data analysis platforms across radiation oncology centres. Methods A distributed learning network of computer systems is presented, with software tools to extract and report on oncology data and to enable statistical model development. A distributed or federated learning approach keeps data in the local centre, but models are developed from the entire cohort. Results The feasibility of this approach is demonstrated across six Australian oncology centres, using routinely collected lung cancer data from oncology information systems. The infrastructure was used to validate and develop machine learning for model-based clinical decision support and for one centre to assess patient eligibility criteria for two major lung cancer radiotherapy clinical trials (RTOG-9410, RTOG-0617). External validation of a 2-year overall survival model for non-small cell lung cancer (NSCLC) gave an AUC of 0.65 and C-index of 0.62 across the network. For one centre, 65% of Stage III NSCLC patients did not meet eligibility criteria for either of the two practice-changing clinical trials, and these patients had poorer survival than eligible patients (10.6 m vs. 15.8 m, P = 0.024). Conclusion Population-based studies on routine data are possible using a distributed learning approach. This has the potential for decision support models for patients for whom supporting clinical trial evidence is not applicable.

Aim To evaluate patient choice of prostate cancer radiotherapy fractionation, using a decision aid. Background Recent ASTRO guidelines recommend patients with localised prostate cancer be offered moderately hypofractionated radiation therapy after discussing increased acute toxicity and uncertainty of long-term results compared to conventional fractionation. Materials and methods A decision aid was designed to outline the benefits and potential downsides of conventionally and moderately hypofractionated radiation therapy. The aid incorporated the ASTRO guideline to outline risks and benefits. Results In all, 124 patients with localised prostate cancer were seen from June-December 2018. Median age was 72 (range 50–90), 49.6 % were intermediate risk (50.4 % high risk). All except three patients made a choice using the aid; the three undecided patients were hypofractionated. In all, 33.9 % of patients chose hypofractionation: falling to 25.3 % for patients under 75 years, 24.3 % for patients living within 30 miles of the cancer centre, and 14.3 % for patients with baseline gastrointestinal symptoms. On multivariate analysis, younger age, proximity to the centre, and having baseline gastrointestinal symptoms significantly predicted for choosing conventional fractionation. Insurance status, attending clinician, baseline genitourinary symptoms, work/carer status, ECOG, cancer risk group and driving status did not impact choice. Reasons for choosing conventional fractionation were certainty of long-term results (84 %) and lower acute bowel toxicity (51 %). Conclusions Most patients declined the convenience of moderate hypofractionation due to potentially increased acute toxicity, and the uncertainty of long-term outcomes. We advocate that no patient should be offered hypofractionation without a thorough discussion of uncertainty and acute toxicity.

Introduction We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. Methods Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64–66 Gy IG-IMRT to the prostate bed between 2007 and 2015. Results Median follow-up after PPRT was 39 months. Baseline grade ≥2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade ≥2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade ≥4 toxicities. Conclusions Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade ≥2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT.

Purpose Triple negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases and is associated with a poor prognosis. In this retrospective study of patients undergoing radiation therapy as part of their treatment, disease-free survival (DFS) and overall survival (OS) of TNBC patients were examined in relation to clinical and treatment-related factors. Patients and Methods The electronic records of 214 consecutive TNBC patients treated with surgery followed by radiotherapy at the Mid North Coast Cancer Institute between 2006 and 2016 were reviewed. Overall survival and DFS times were analyzed using the Kaplan-Meier method; multivariate Cox proportional hazard regression modelling was used to assess the significance of prognostic factors. Results The majority of tumors were T1 (51.9%), followed by T2 (39.2%) and T3 (6.1%). For the whole group, mean DFS was 106.4 (SD 48.7) months; OS 109.4 (SD 52.1) months. Radiotherapy technique, fractionation protocol and laterality were not significant factors for DFS or OS (p>0.05). However, compared to breast conservation, mastectomy was associated with poorer DFS (mean 114.2 vs 65.2 months; p 5cm and positive nodal status is associated with poorer DFS in TNBC patients. Radiotherapy technique or fractionation protocol were not associated with differences in DFS or OS in our patient cohort.

Cancers of the skin (the majority of which are basal and squamous cell skin carcinomas, but also include the rarer Merkel cell carcinoma) are overwhelmingly the most common of all types of cancer. Most of these are treated surgically, with radiation reserved for those patients with high risk features or anatomical locations less suitable for surgery. Given the high incidence of both basal and squamous cell carcinomas, as well as the relatively poor outcome for Merkel cell carcinoma, it is useful to investigate the role of other disciplines regarding their diagnosis, staging and treatment. Mathematical modelling is one such area of investigation. The use of mathematical modelling is a relatively recent addition to the armamentarium of cancer treatment. It has long been recognised that tumour growth and treatment response is a complex, non-linear biological phenomenon with many mechanisms yet to be understood. Despite decades of research, including clinical, population and basic science approaches, we continue to be challenged by the complexity, heterogeneity and adaptability of tumours, both in individual patients in the oncology clinic and across wider patient populations. Prospective clinical trials predominantly focus on average outcome, with little understanding as to why individual patients may or may not respond. The use of mathematical models may lead to a greater understanding of tumour initiation, growth dynamics and treatment response.

Purpose/objectives There are no published reports of prostate specific membrane antigen (PSMA) positron emission tomography (PET) guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) in newly diagnosed lymph node (LN) positive prostate cancer. We report early toxicity and efficacy outcomes with this approach. Materials/methods Patients with newly diagnosed high-risk prostate cancer were staged using PSMA PET, computed tomography (CT) and bone scans. Patients with LN positive-only metastases were offered curative therapy using 3 months androgen deprivation therapy (ADT) followed by DE-IMRT (using volumetric arc therapy), and 3 years adjuvant ADT. All patients had fiducial marker insertion, with privately insured patients having spacer hydrogel insertion. PET and prostate magnetic resonance imaging were fused with the planning CT. We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45Fx to bilateral elective pelvic LNs. Results In all, 46 patients were treated, with 83% Gleason 8–10, 67% T3/T4, median number of LNs 2 (range 1–6), and median PET-positive LN volume 1.14 cc (range 0.15–4.14). LNs were outside of standard contouring guidelines in 37% of patients. The mean PET-positive LN clinical target volume dose ranged from 73.3 to 85.9 Gy (median 83.6 Gy). With 24 months median follow-up, two year failure-free survival was 100%, and 2 year overall survival 95.7%. Acute grade 1 and 2 GI toxicity occurred in 48 and 11% of patients, and GU toxicity in 72 and 24%. Late grade 1, 2 and 3 GI toxicity occurred in 13, 2 and 0%, and GU toxicity 28, 13 and 4%. No toxicity was attributable to the high dose LN boost. Conclusions PSMA PET-guided DE-IMRT up to 81 Gy to the prostate and involved LNs, and long term ADT, is a promising approach for newly diagnosed LN positive prostate cancer. LN contouring guidelines require re-evaluation in the era of PSMA PET imaging.

Aim To develop and apply a clinical incident taxonomy for radiation therapy. Background Capturing clinical incident information that focuses on near-miss events is critical for achieving higher levels of safety and reliability. Methods and materials A clinical incident taxonomy for radiation therapy was established; coding categories were prescription, consent, simulation, voluming, dosimetry, treatment, bolus, shielding, imaging, quality assurance and coordination of care. The taxonomy was applied to all clinical incidents occurring at three integrated cancer centres for the years 2011–2015. Incidents were managed locally, audited and feedback disseminated to all centres. Results Across the five years the total incident rate (per 100 courses) was 8.54; the radiotherapy-specific coded rate was 6.71. The rate of true adverse events (unintended treatment and potential patient harm) was 1.06. Adverse events, where no harm was identified, occurred at a rate of 2.76 per 100 courses. Despite workload increases, overall and actual rates both exhibited downward trends over the 5-year period. The taxonomy captured previously unidentified quality assurance failures; centre-specific issues that contributed to variations in incident trends were also identified. Conclusions The application of a taxonomy developed for radiation therapy enhances incident investigation and facilitates strategic interventions. The practice appears to be effective in our institution and contributes to the safety culture. The ratio of near miss to actual incidents could serve as a possible measure of incident reporting culture and could be incorporated into large scale incident reporting systems.

Moss tissue chemistry is widely used as a bioindicator of atmospheric deposition. The objective of this study was to compare the tissue chemistry of two moss species in Irish Atlantic oak woodlands, Isothecium myosuroides [Im] and Thuidium tamariscinum [Tt], and to determine their relationship to indices of atmospheric deposition. Moss species were collected from twenty-two woodland sites during April 2013 and analysed for nitrogen, sulphur, and eleven heavy metals. Nitrogen content was significantly correlated between species (rs = 0.84), but their mean values (Im = 1.23%, Tt = 1.34%) were significantly different. A simple linear regression suggested that nitrogen content was significantly related to atmospheric ammonia (R2 = 0.67 [Im], R2 = 0.65 [Tt]) and total nitrogen deposition (R2 = 0.57 [Im], R2 = 0.54 [Tt]). Many heavy metals had significant interspecies correlations (Al, V, Ni, Cu, Zn, As, Sb, Pb; rs = 0.46−0.77). A few metals (As, Sb and Pb) were positively correlated with easting and northing for both species, which may suggest transboundary or national industrial emissions sources. The results suggest that both species could be used as bioindicators of deposition for nitrogen and some heavy metals, although further study of the relationship between tissue concentrations and atmospheric deposition is warranted. Furthermore, interspecies calibration is required to use both species in conjunction.

The activities associated with urbanization, such as vehicular traffic and industrial processes, lead to elevated emissions of atmospheric pollutants. Measuring the spatial extent of these pollutants is pivotal to identifying areas of concern and assessing mitigation measures. The objective of this study was to evaluate the relative deposition of heavy metals and nitrogen using moss species along an urban–agricultural transition in the Credit River Watershed, southern Ontario. Thirteen species of moss were collected from Sugar Maple (Acer saccharum) dominated forest stands across the study area, with only one moss species (Atrichum altercristatum) commonly occurring. Heavy metal concentrations were variable between species; the Coefficient of Variation (CV) for the majority of metals (Al, V, Cr, Fe, Ni, As, Sb and Pb) was greater than ~50% across species. Nonetheless, metals exhibited similar trends, with the highest concentrations for Fe, followed by Al > Zn > Cu > Pb > Cr > Ni > V > As > Cd > Sb > Hg across species. Heavy metal concentrations in Atrichum altercristatum exhibited lower variability between sites, with CV < 33% for most metals (Cu, Zn, As, Cd, Sb, Pb and Hg). Further, many metal concentrations were strongly correlated (e.g., Al, V, Cr, Fe, and As; r ≤ 0.90) suggesting common emission sources, such as wind blown dust from agricultural activities or vehicular traffic, both predominant throughout the watershed.

Introduction We compare the results of modern external-beam radiotherapy (EBRT), using combined androgen deprivation and dose-escalated intensity-modulated radiotherapy with MRI-CT fusion and daily image guidance with fiducial markers (DE-IG-IMRT), with recently published Australian series of brachytherapy and surgery. Methods Five-year actuarial biochemical disease-free survival (bDFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCaSS) were calculated for 675 patients treated with DE-IG-IMRT and androgen deprivation therapy (ADT). Patients had intermediate-risk (IR) and high-risk (HR) disease. A search was conducted identifying Australian reports from 2005 onwards of IR and HR patients treated with surgery or brachytherapy, reporting actuarial outcomes at 3 years or later. Results With a median follow-up of 59 months, our 5-year bDFS was 93.3% overall: 95.5% for IR and 91.3% for HR disease. MFS was 96.9% overall (99.0% IR, 94.9% HR), and PCaSS was 98.8% overall (100% IR, 97.7% HR). Prevalence of Grade 2 genitourinary and gastrointestinal toxicity at 5 years was 1.3% and 1.6%, with 0.3% Grade 3 genitourinary toxicity and no Grade 3 gastrointestinal toxicity. Eight reports of brachytherapy and surgery were identified. The HDR brachytherapy series' median 5-year bDFS was 82.5%, MFS 90.0% and PCaSS 97.9%. One surgical series reported 5-year bDFS of 65.5% for HR patients. One LDR series reported 5-year bDFS of 85% for IR patients. Conclusions Modern EBRT is at least as effective as modern Australian surgical and brachytherapy techniques. All patients considering treatment for localised prostate cancer should be referred to a radiation oncologist to discuss EBRT as an equivalent option.

Aims Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity-modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT. Methods The records of 509 consecutive patients with planning MRI scans being treated with IMRT for prostate cancer between January 2010 and July 2012 were retrospectively reviewed. Tumor staging and treatment plans before and after MRI were compared. Results Of the 509 patients, 103 (20%) were upstaged and 44 (9%) were migrated to a higher risk category as a result of findings at MRI. In 94 of 509 patients (18%), the MRI findings altered management. Ninety-four of 509 patients (18%) had a change to their clinical target volume (CTV) or treatment technique, and in 41 of 509 patients (8%) the duration of hormone therapy was changed because of MRI findings. Conclusion The use of radiotherapy planning MRI altered CTV design, dose and/or duration of androgen deprivation in 18% of patients in this large, single institution series of men planned for dose-escalated prostate IMRT. This has substantial implications for radiotherapy target volumes and doses, as well as duration of androgen deprivation. Further research is required to investigate whether newer MRI techniques can simultaneously fulfill staging and radiotherapy contouring roles.

Aim The use of complementary and alternative therapies (CAT) in oncology patients is increasing in incidence, with calls to routinely screen for their use. We introduced a screening tool as part of clinical care to identify CAT use. Methods We evaluated all patients who attended the radiation oncology outpatient clinic between December 2011 and July 2012, who had filled out the CAT screening tool, and evaluated types of CAT use, reasons for use and predictors of CAT usage. Results A total of 639 patients completed the CAT screening tool, which was 75% of eligible patients. There were 464 (72.6%) men and 175 (27.4%) women, with a mean age of 69.9 years (range 27–94 years). Prostate cancer was the predominant diagnosis (53.1%), followed by breast cancer (17.5%) and skin cancer (14.7%). Of these, 530 patients (82.9%) had used at least one therapy. Of the 530 patients using CAT, the most quoted reasons for use were to improve quality of life (42.6%), to boost the immune system and general health (33.6%), to increase energy levels (32.6%) and to live longer (28.9%). Of the 530 users, only 112 patients (21.1%) took CAT to help cure their cancer. Women were significantly more likely to use CAT, as were patients with breast cancer. Conclusions The use of CAT in patients with cancer is prevalent and more frequent in our population than in other published studies. Few patients use CAT to improve their cancer cure, but rather use CAT for other reasons.

Purpose Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. Results There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD ( P Conclusion Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.

Introduction Decision regret (DR) may occur when a patient believes their outcome would have been better if they had decided differently about their management. Although some studies investigate DR after treatment for localised prostate cancer, none report DR in patients undergoing surgery and post-prostatectomy radiotherapy. We evaluated DR in this group of patients overall, and for specific components of therapy. Methods We surveyed 83 patients, with minimum 5 years follow-up, treated with radical prostatectomy (RP) and post-prostatectomy image-guided intensity-modulated radiotherapy (IG-IMRT) to 64–66 Gy following www.EviQ.org.au protocols. A validated questionnaire identified DR if men either indicated that they would have been better off had they chosen another treatment, or they wished they could change their mind about treatment. Results There was an 85.5% response rate, with median follow-up post-IMRT 78 months. Adjuvant IG-IMRT was used in 28% of patients, salvage in 72% and ADT in 48%. A total of 70% of patients remained disease-free. Overall, 16.9% of patients expressed DR for treatment, with fourfold more regret for the RP component of treatment compared to radiotherapy (16.9% vs 4.2%, P = 0.01). DR for androgen deprivation was 14.3%. Patients were regretful of surgery due to toxicity, not being adequately informed about radiotherapy as an alternative, positive margins and surgery costs (83%, 33%, 25% and 8% of regretful patients respectively). Toxicity caused DR in the three radiotherapy-regretful and four ADT-regretful patients. Patients were twice as regretful overall, and of surgery, for salvage vs adjuvant approaches (both 19.6% vs 10.0%). Conclusion Decision regret after RP and post-prostatectomy IG-IMRT is uncommon, although patients regret RP more than post-operative IG-IMRT. This should reassure urologists referring patients for post-prostatectomy IG-IMRT, particularly in the immediate adjuvant setting. Other implications include appropriate patient selection for RP (and obtaining clear margins), and ensuring adequately discussing definitive radiotherapy as an alternative to surgery.

Thomas P Shakespeare,1,2 Shea W Wilcox,1 Noel J Aherne1,2 1Department of Radiation Oncology, North Coast Cancer Institute, 2Rural Clinical School, Faculty of Medicine, University of New South Wales, Coffs Harbour, NSW, Australia Aim: Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74Gy. We aimed to determine whether DE-EBRT >74Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods: Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6months neoadjuvant ADT and DE-EBRT, followed by 2years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74Gy to 76Gy and then to 78Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results: In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74Gy, 76Gy, and 78Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion: There was no benefit of DE-EBRT >74Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. Keywords: radiotherapy, IMRT, dose, dose escalation, dose de-escalation, androgen deprivation therapy, prostate cancer

Thomas P Shakespeare,1,2 Shea W Wilcox,1 Noel J Aherne1,2 1Department of Radiation Oncology, North Coast Cancer Institute, 2Faculty of Medicine, Rural Clinical School, The University of New South Wales, Coffs Harbour, New South Wales, Australia Background: Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve the outcomes in patients with intermediate-risk prostate cancer. Despite this, there are only few reports evaluating DE-EBRT for patients with intermediate-risk prostate cancer receiving neoadjuvant ADT, and virtually no studies investigating dose escalation >74Gy in this setting. We aimed to determine whether DE-EBRT >74Gy improved the outcomes for patients with intermediate-risk prostate cancer who received neoadjuvant ADT. Findings: In our institution, patients with intermediate-risk prostate cancer were treated with neoadjuvant ADT and DE-EBRT, with doses sequentially increasing from 74Gy to 76Gy and then to 78Gy between 2006 and 2012. We identified 435 patients treated with DE-EBRT and ADT, with a median follow-up of 70months. For the 74Gy, 76Gy, and 78Gy groups, five-year biochemical disease-free survival rates were 95.0%, 97.8%, and 95.3%, respectively; metastasis-free survival rates were 99.1%, 100.0%, and 98.6%, respectively; and prostate cancer-specific survival rate was 100% for all three dose levels. There was no significant benefit for dose escalation either on univariate or multivariate analysis for any outcome. Conclusion: There was no benefit for DE-EBRT >74Gy in our cohort of intermediate-risk prostate cancer patients treated with neoadjuvant ADT. Given the higher risks of toxicity associated with dose escalation, it may be feasible to omit dose escalation in this group of patients. Randomized studies evaluating dose de-escalation should be considered. Keywords: radiotherapy, IMRT, dose, dose escalation, dose de-escalation, androgen deprivation therapy, prostate cancer

The role of adjuvant radiotherapy in thymic tumors has not been explicitly defined. Since epithelial thymic tumors are relatively radiosensitive, many clinicians advocate the use of adjuvant radiation therapy in all cases, in addition to those cases where there is extension beyond the capsule [1]–[4]. Justification for adjuvant radiation is based on studies showing decreased recurrence rates for stage II disease with adjuvant therapy from 30% to 5% [5, 6]. Other groups suggest that, due to the low incidence of local recurrence after complete resection of stage II thymomas, radiation therapy should be reserved for selected patients [7]–[10]. Schmidt-Wolf [11] proposed that adjuvant external-beam radiotherapy should be considered only for stages II and III disease where there were extensive adhesions between tumor and pleura, microscopic pleural infiltration, or macroscopic invasion of the pericardium, large vessels, or lung. In addition, Chen [12] noted that completely resected stage II thymomas of WHO subtype A, AB, and B–I may not require adjuvant therapy.

Aims To report cancer-specific and health-related quality-of-life outcomes in patients undergoing radical chemoradiation (CRT) alone for oesophageal cancer. Materials and methods Between 1998 and 2005, 56 patients with oesophageal cancer received definitive radical CRT, due to local disease extent, poor general health, or patient choice. Data from European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, and at 3, 6 and 12 months after CRT where applicable. Results The median follow-up was 18 months. The median overall survival was 14 months, with a 51, 26 and 13% 1-, 3- and 5-year survival, respectively. At 12 months after treatment there was a significant improvement compared with before treatment with respect to dysphagia and pain. Global health scores were not significantly affected. Conclusions Considering the relatively short long-term survival for this cohort of patients, maximising the quality of those final months should be very carefully borne in mind from the outset. The health-related quality-of-life data reported herein helps to establish benchmarks for larger evaluation within randomised clinical trials.

The critical load approach to emission reductions has become an important element of the United Nations Economic Commission for Europe (UNECE) Convention on Long-Range Transboundary Air Pollution (CLRTAP). The steady state mass balance approach (SSMB) is the most widely used method in Europe for estimating critical loads, typically applied to forest ecosystems on mineral soils in conjunction with a base cation to aluminium (Bc:Al) ratio using a default critical limit of 1.0. The 'typical' approach has been expanded in this paper by: inclusion of a broader range of natural and semi-natural receptor ecosystems; inclusion of multiple chemical criterion for each receptor; and an attempt to include organic soils (peatlands). Critical loads of acidity were estimated for the Republic of Ireland using four receptor ecosystems (coniferous forest, deciduous forest, natural grasslands and moors and heathlands) and seven chemical criteria. The dominant chemical criteria, in the determination of critical loads, were based on a critical pH limit for mineral soils or a critical pH shift in relation to pristine conditions for organic soils. Approximately 68 and 26% of the final distribution of critical loads were estimated using these criteria, respectively. The 5th-percentile critical loads of acidity were more sensitive than those previously estimated for Ireland due to the inclusion of organic soils. Furthermore, coniferous ecosystems had the lowest critical loads due to the high percentage occurring on organic soils, and the removal of base cations through harvesting. The results demonstrate that it may be more appropriate to use multiple criteria and receptors to ensure adequate protection of biological indicators. However, it is important that appropriate critical limits are chosen to protect the biological indicators and receptor ecosystems from long-term damage.

Shea W Wilcox,1,4 Noel J Aherne,2,4 Linus C Benjamin,1 Bosco Wu,1 Thomaz de Campos Silva,3 Craig S McLachlan,4 Michael J McKay,3,5 Andrew J Last,1 Thomas P Shakespeare1–4 1North Coast Cancer Institute, Port Macquarie, NSW, Australia; 2North Coast Cancer Institute, Coffs Harbour, NSW, Australia; 3North Coast Cancer Institute, Lismore, NSW, Australia; 4The University of New South Wales, Rural Clinical School, Sydney, NSW, Australia; 5The University of Sydney, Sydney, NSW, Australia Purpose: Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Methods and materials: Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results: Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. Conclusion: There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer. Keywords: dose-escalation, image-guided radiotherapy, treatment related toxicity, biochemical disease-free survival&nbsp

The use of complementary and alternative therapies (CAT) in oncology patients is increasing in incidence, with calls to routinely screen for their use. We introduced a screening tool as part of clinical care to identify CAT use.We evaluated all patients who attended the radiation oncology outpatient clinic between December 2011 and July 2012, who had filled out the CAT screening tool, and evaluated types of CAT use, reasons for use and predictors of CAT usage.A total of 639 patients completed the CAT screening tool, which was 75% of eligible patients. There were 464 (72.6%) men and 175 (27.4%) women, with a mean age of 69.9 years (range 27-94 years). Prostate cancer was the predominant diagnosis (53.1%), followed by breast cancer (17.5%) and skin cancer (14.7%). Of these, 530 patients (82.9%) had used at least one therapy. Of the 530 patients using CAT, the most quoted reasons for use were to improve quality of life (42.6%), to boost the immune system and general health (33.6%), to increase energy levels (32.6%) and to live longer (28.9%). Of the 530 users, only 112 patients (21.1%) took CAT to help cure their cancer. Women were significantly more likely to use CAT, as were patients with breast cancer.The use of CAT in patients with cancer is prevalent and more frequent in our population than in other published studies. Few patients use CAT to improve their cancer cure, but rather use CAT for other reasons.