Stereotactic ablative body radiation therapy for isolated pulmonary metastases from pancreatic cancer after metastectomy with positive margins: a case report.

BACKGROUND: Isolated pulmonary oligometastases as the first site of dissemination after initial resection of pancreatic ductal adenocarcinoma (PC) is a rare event, and the treatment in this subgroup is challenging. Recurrence in the lung after initial primary tumour resection is associated with the most long-term survivors of patients with metastatic PC. Stereotactic ablative body radiation therapy (SABR) or metastectomy for pulmonary oligometastases from PC is becoming more common. However, patients with close or positive margins after metastectomy for isolated pulmonary metastatic PC are at high risk for recurrence. This requires a treatment capable of achieving high rates of local control and improved quality of life by delaying the need for systemic chemotherapy. In other settings, SABR has been shown to achieve these goals, allowing safe dose escalation with excellent conformity and short duration of treatment. CASE PRESENTATION: We report the case of a 48-year old Caucasian man with a history of locally advanced PC initially treated with neoadjuvant chemotherapy followed by Whipple's resection in August 2016. After a disease-free interval of 3 years, he developed three isolated pulmonary metastases which were treated with local resection. In the setting of microscopically positive resection margins (R1), adjuvant lung SABR was delivered to all three sites. His treated lung disease remained radiologically stable for up to twenty months after SABR. Treatment was well tolerated. In January 2021, he developed a malignant pre-tracheal node which was treated with conventionally fractionated radiotherapy and remained controlled for the duration of follow-up. A year later, he developed widespread metastatic disease including pleura, bone and adrenal gland, together with presumed progression in one of the original lung lesions, receiving palliative radiotherapy for right chest wall pain. He was later found to have an intracranial metastasis and died in February 2022, 5½ years after initial treatment. CONCLUSION: We present the case of a patient treated with SABR after R1 resection of 3 isolated pulmonary metastases from PC, with no treatment toxicities and durable local control. For well-selected patients in this setting, adjuvant lung SABR may be a safe and effective treatment option.

Research culture in Australian and New Zealand radiation oncology: Fact or fantasy?

INTRODUCTION: Fostering a research culture is a key goal of the Royal Australian and New Zealand College of Radiologists, yet there has never been an organization-wide enquiry into the extent to which this is being realized. The purpose of this work was to address that deficit for the Radiation Oncology (RO) Faculty to serve as a baseline for future comparison. The hypothesis was that such a culture is closer to fact than fantasy. METHODS: With College approval, three de-identified Excel spreadsheets detailing 25 research-related sub-categories of the Faculty's Continuing Professional Development (CPD) database were interrogated for the 2019-21 triennium, accepting that research activity in 2020-21 would be COVID-19 suppressed. The numbers obligated to self-report CPD were 482, 496 and 511, respectively. Primary endpoints were the percentages of ROs claiming at least one research-related activity overall, and in each of the sub-categories individually, by year. Secondary endpoints were the "breadth" (number of sub-categories claimed/individual) and "depth" (percentages solely claiming in one of four lower-level sub-categories), by year. RESULTS: ROs claimed in 23/25 sub-categories. The percentages of ROs claiming at least one research-related activity were 71%, 44%, and 62% in 2019-21, respectively. The median number of sub-categories claimed by these ROs was 2 (range 1-10) in each year. The commonest activity was journal article co-author (25%, 16% and 27%, respectively). For 2019, the most representative year, other common activities were inhouse/local meeting presentation (17%), invited lecture at state level or above (15%), manuscript peer review and research project principal investigator (14% each). The percentages of ROs solely claiming in one lower-level activity ranged between 4.4% and 5.9% per year. CONCLUSION: A culture of research is arguably more fact than fantasy in ANZ. It is likely that Faculty curriculum requirements, research funding and other promotional initiatives have contributed substantively to this.

Cochlear sparing in LINAC-based radiosurgery for vestibular schwannoma: a dosimetric comparison of dynamic conformal arc, IMRT and VMAT treatment plans.

BACKGROUND: Stereotactic radiosurgery (SRS) is the preferred treatment for vestibular schwannoma (VS) in patients with preserved hearing and tumour diameter < 3 cm. Emerging evidence suggests restricting cochlear dose could preserve hearing. This retrospective replanning study aims to compare dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for superiority of cochlear dose sparing without compromising tumour coverage. METHODS: Eligibility criteria included sporadic VS, serviceable hearing and availability of CT and MRI for planning. The original gross tumour volume and brainstem OAR volume were retained; the cochlea was newly contoured on the planning CT scan (bone window). Each case was replanned using the three above techniques, prescribing 12 Gy to the 80% isodose line. No dose constraint was applied to the cochlea. RESULTS: Eighteen patients were replanned. Mean tumour volume was 2.25 cc. Tumour coverage and tumour mean dose (DCAT: 14.2, IMRT: 14.6, VMAT: 14.5 Gy) were comparable. Paddick and RTOG conformity indices were better for DCAT (0.66 and 1.6) and VMAT (0.69 and 1.5) compared to IMRT (0.56 and 1.9). DCAT had superior gradient index (3.0) compared to VMAT (3.4) and IMRT (3.4). VMAT delivered the lowest mean brainstem maximum dose (8.3 Gy) and decreased the mean cochlear dose (3.4 Gy) by 2.3 and 2.1 Gy, and the mean cochlear maximum dose (3.6 Gy) by 2.4 and 2.5 Gy relative to DCAT and IMRT, respectively. CONCLUSION: LINAC-based SRS treatment using VMAT can achieve better cochlear dose sparing than DCAT or IMRT while maintaining tumour coverage.

The Effect of Cochlear Dose on Hearing Preservation After Low-Dose Stereotactic Radiosurgery for Vestibular Schwannomas: A Systematic Review.

Purpose: Despite excellent tumor control after stereotactic radiosurgery (SRS) for vestibular schwannoma (VS), the hearing preservation rate remains unsatisfactorily low. Although many factors have been associated with hearing loss, the dose to cochlea has gained more interest in recent years. However, studies investigating the relation between cochlear dose and hearing outcomes have produced inconsistent results. The purpose of this work is to systematically review the literature and critically analyze the studies that investigated the correlation between cochlear dose and hearing loss. Methods and Materials: A literature search of Ovid MEDLINE, Embase, and Scopus was performed. Studies were included if the SRS dose used was 11 to 14 Gy and included adult patients with sporadic VS, initially serviceable hearing, and at least 24 months of mean or median follow-up. Results: Twenty-one cohort studies and 1 case-control study were eligible for inclusion, and none were considered to be truly prospective. There was substantial heterogeneity between studies in terms of baseline hearing status, cochlear dosimetry, definition and reporting of hearing outcome, and duration of follow-up, limiting comparison between studies and precluding formal meta-analysis. Eleven studies showed a statistically significant correlation between cochlear dose and hearing outcome, but there was considerable variation in the reported cochlear dose parameter that predicted hearing outcome and whether it was an independent predictor. The definition of hearing outcome and whether the outcome variable is continuous or dichotomous have a bearing on the reported correlation between cochlear dose and hearing outcome. Conclusions: Whether cochlear dose is a predictor of hearing preservation after SRS for VS could not be unequivocally determined. Future studies should use consistent cochlear dosimetry and hearing outcomes for reliable assessment. In the meantime, based on currently available data, a practical approach will be to aim for a mean cochlear dose <4 to 6 Gy without compromising tumor dose.

Impact of Radiation Oncology Research Grants Awarded by the Royal Australian and New Zealand College of Radiologists Using the "Payback Framework".

PURPOSE: Radiation Oncology (RO) societies which provide research grants from membership dues or charitable donations owe it to their funders to assess value for money, yet very little has been published on the outcomes of such grants. A previous Royal Australian and New Zealand College of Radiologists (RANZCR) survey confirmed significant academic impact from their RO grants. The purpose of this work was to update and broaden the survey using, to our knowledge for the first time in the RO literature, the "Payback Framework", a model employed extensively elsewhere in health research. METHODS AND MATERIALS: Between funding years 2010 and 2020, 58 grants were awarded to 41 individuals, median 1 per individual (range 1-4), median AUD $20,000 (US $14,000) per grant (range AUD $5,000-$26,000). Five recipients of failed projects were excluded. The remaining 36 individuals, receiving 51 grants totaling US $660,000, were eligible for a voluntary on-line survey (SurveyMonkey) assessing project outcomes. Data collection and checking extended to 31 January 2022. RESULTS: The survey response rate was 100% (36/36). Objective academic outcomes attributable, at least in part, to the grants included 103 conference presentations, 59 publications, 21 prizes and 18 higher degrees. 27 consequential grants totaled US $4.5M, a 6.8-fold return on investment. Broader impacts included perceived contributions to guideline development (53% of recipients), changes in clinical decision making (72%) or radiotherapy techniques (61%), enabling of subsequent research (56%), development of novel research tools (19%) and recruitment of research assistant(s) (19%). The three most important factors reported to contribute to project success were the RO grant (83%), networking (81%) and local infrastructure (81%). The grant program was rated very positively. CONCLUSIONS: This updated RANZCR survey has confirmed continuing significant academic output from its RO research grants but has also revealed broader benefits using the Payback Framework. We would encourage other RO societies to report their grant outcomes using a similar framework.

LINAC stereotactic radiosurgery for brain arteriovenous malformations: An updated single centre analysis of outcomes.

Arteriovenous malformations (AVM) of the brain are congenital, high pressure vascular malformations, which are at risk of haemorrhage. Stereotactic radiosurgery (SRS) can obliterate the nidus by delivering a precise high dose of ionising radiation in a single fraction. This paper updates long term AVM obliteration rates, time to obliteration and retreatment outcomes in LINAC delivered SRS treatment at the Royal Adelaide Hospital. A retrospective review of a prospectively maintained AVM SRS database supplemented by clinical case notes, patient correspondence and electronic medical records was performed. 89 AVMs received primary SRS treatment for which the crude obliteration rate was 61% (68% for 79 patients with adequate follow up). Higher marginal dose, smaller nidus size and lower Pollock-Flickinger (PF) score were significantly associated with AVM obliteration. The crude obliteration rates for patients with adequate follow-up and AVM diameter < 3 cm vs ≥ 3 cm were 76% vs 48%, respectively, and 93% with PF score < 1.0. Median time to obliteration was 36 months. Higher dose and lower PF score were associated with earlier obliteration. The crude obliteration rate after second SRS was 56% (9/16 patients) and no significant associations were found. These obliteration rates after primary and retreatment LINAC SRS are comparable to other studies. Marginal dose and PF score were the main predictors of obliteration overall as well as early (<36 months) obliteration.

Adult medulloblastoma in an Australian population.

Medulloblastoma in adult patients is a rare condition with limited contemporary demographic and treatment outcome data available in an Australian population. We conducted a retrospective review of patterns of care and outcomes of adult patients diagnosed with medulloblastoma treated at major neuro-oncology centres across Australia between January 2010 and December 2019. A total of 80 patients were identified and the median follow-up after diagnosis was 59.2 (range 0.5-204) months. A variety of chemotherapy regimens were used in the adjuvant and recurrent settings. The median overall survival (mOS) was 78 months (IQR 17.5-94.8). Patients who had no residual disease post-resection or with SHH-subtype tumours had a numerically longer 5-year survival rate than those with residual disease post resection or non-SHH subtypes respectively. The median time to recurrence from diagnosis was 18.4 months. The median OS from 1st relapse was 22.1 months (95% CI 11.7-31.4) and mOS from second relapse was 10.2 months (95% CI 6.6 - NR). This is the largest dataset examining patterns of care of adult patients with medulloblastoma in an Australian population. Substantial variation existed in the chemotherapy agents used in the adjuvant and recurrent setting. As has been demonstrated in a paediatric population, trials such as the upcoming EORTC 1634-BTG/NOA-23 trial (PersoMed-1 study) which are tailoring treatments to molecular profiles are likely to improve outcome in adult medulloblastoma.

Prognostic factors for survival and ambulatory status at 8 weeks with metastatic spinal cord compression in the SCORAD randomised trial.

BACKGROUND: Metastatic spinal cord compression (MSCC) carries a poor prognosis and management is based on the likelihood of maintaining mobility and predicted survival. PATIENTS AND METHOD: SCORAD is a randomised trial of 686 patients comparing a single dose of 8 Gy radiotherapy with 20 Gy in 5 fractions. Data was split into a training set (412, 60%) and a validation set (274, 40%). A multivariable Cox regression for overall survival (OS) and a logistic regression for ambulatory status at 8 weeks were performed in the training set using baseline factors and a backward selection regression to identify a parsimonious model with p ≤ 0.10. Receiver Operating Characteristic (ROC) analysis evaluated model prognostic performance in the validation set. Validation of the final survival model was performed in a separate registry dataset (n = 348). RESULTS: The survival Cox model identified male gender, lung, gastrointestinal, and other types of cancer, compression at C1-T12, presence of non-skeletal metastases and poor ambulatory status all significantly associated with worse OS (all p < 0.05). The ROC AUC for the selected model was 75% (95%CI: 69-81) in the SCORAD validation set and 68% (95%CI: 62-74) in the external validation registry data. The logistic model for ambulatory outcome identified primary tumour breast or prostate, ambulatory status grade 1 or 2, bladder function normal and prior chemotherapy all significantly associated with increased odds of ambulation at 8 weeks (all p < 0.05). The ROC AUC for the selected model was 72.3% (95% CI 62.6-82.0) in the validation set. CONCLUSIONS: Primary breast or prostate cancer, and good ambulatory status at presentation, are favourable prognostic factors for both survival and ambulation after treatment.

Establishing a palliative Advanced Practice Radiation Therapist role: A viable alternative to a Rapid Access Palliative Radiation Therapy clinic in Australia.

INTRODUCTION: A recent survey found that Rapid Access Palliative Radiation Therapy (RAPRT) clinics have not been widely embraced in Australia and New Zealand for many reasons. The purpose of this narrative is to describe the transition of a Brisbane, Queensland, RAPRT clinic to an Advanced Practice Radiation Therapist (APRT) model to further improve access and delivery of palliative radiation therapy at that centre. METHODS: The weekly RAPRT clinic commenced in 2005, run by one Radiation Oncologist (RO). The role of the attending senior Radiation Therapist (RT) was mainly to facilitate rapid passage of patients from clinic to treatment. However, because individual ROs preferred to retain care of their own patients, capture of the relevant population was limited. It was therefore decided in 2012 to gradually transition to a model where the RT would work with all ROs and manage all palliative patients from referral to follow-up, under RO supervision. RESULTS: The steps to this palliative APRT pathway involved formulation of the role description, mentoring/training of the RT, overseas site visits, further post-graduate education, funding of the position, staff feedback surveys, evaluation studies and endorsement by professional bodies, leading to formal credentialing in 2017. Importantly, the APRT undertakes all steps in the pathway including field or volume delineation (with approval and sign-off by the responsible RO). The role has come to be highly valued by all disciplines. CONCLUSION: The successful establishment of a palliative APRT role in one Australian centre serves as a template for others wishing to create a similar position.

Rapid Access Palliative Radiation Therapy Clinics: The Evidence Is There, but Where Are the Clinics? An Australian and New Zealand Perspective.

PURPOSE: First developed in Canada in the 1990s, Rapid Access Palliative Radiation Therapy (RAPRT) clinics have subsequently spread internationally to expedite treatment for near end-of-life patients, sparing them the need for multiple visits to the department. A "classical" RAPRT clinic is herein defined as "a dedicated clinic specifically established to enable (ideally) same day consultation, planning for, and delivery of palliative radiation treatment." The aim of this work was to determine the current status of these clinics in Australia and New Zealand (ANZ). METHODS AND MATERIALS: A phone survey of all 100 Australian and 10 NZ radiation therapy centers was conducted in March and April 2021. The Chief Medical Officers of the 2 large private practices (GenesisCare and Icon) also approved the survey and answered on behalf of their 57 centers. A single page questionnaire was used, seeking information on the logistics and clinical details of past and present RAPRT clinics, and reasons why other centers do not have one. RESULTS: The survey response rate was 100%. There are only 3 current RAPRT clinics (2.7%). The dominant treatment indication is bone metastases (85%-90%), with most patients receiving single fractions (60%-90%), but commencement on the same day is variable (35%-90%). Five other clinics (4.5%) closed after 4 months to 7 years, but the clinical features were similar. By far, the most common reason (95%) given by the 107 centers without a current RAPRT clinic was that these patients are accommodated using existing resources. CONCLUSIONS: Classical RAPRT clinics have not been widely embraced in ANZ. There are alternative strategies such as the Advanced Practice Radiation Therapist model and techniques to avoid the conventional computed tomography-simulation step, which may also expedite treatment for palliative patients.

Prospective Phase II trial of radiation therapy in localised non-gastric marginal zone lymphoma with prospective evaluation of autoimmunity and Helicobacter pylori status: TROG 05.02/ALLG NHL15.

BACKGROUND: This Phase 2 multicentre trial in localised non-gastric marginal zone lymphoma (MZL) evaluated the effectiveness and safety of radiotherapy and documented markers of autoimmunity and Helicobacter pylori infection. PATIENTS AND METHODS: Eligible patients had Stages I and II or paired-organ, non-gastric MZL. Bone marrow evaluation, autoantibody panel, and H. pylori evaluation were mandatory. Involved-field or involved-site radiotherapy was delivered to 24-30.6 Gy. Detected H. pylori infections underwent eradication. RESULTS: Between 2006 and 2014, six centres enrolled 70 patients, and 68 commenced treatment. The median age was 59 (range: 23-84) years, and 31 (46%) were male. Overall, 55 patients had Stage I disease, nine patients had Stage II disease, and four patients had paired organ-confined disease. Involved extranodal sites with three or more cases were orbital (n = 18), conjunctiva (n = 13), lacrimal (n = 8), skin (n = 8), salivary (n = 7), and muscle (n = 4). Eight patients had primary nodal MZL. At the median follow-up of 5 years (range 0.7-9.4), progression-free survival and overall survival were 79% and 95%, respectively. One lymphoma-related death and two in-field failures (after 25 and 30 Gy, respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2), duodenum, stomach, muscle, and conjunctiva (1 each). No paired-organ MZL relapsed. Apart from cataracts (n = 18), only three treatment-related late grade ≥3 adverse events occurred. Autoantibodies or autoimmune events were detected in 26 of 68 patients (38%). H. pylori infection was detected in 15 of 63 patients (24%) tested. Neither autoimmunity nor H. pylori was detected in 27 of 68 patients (40%). CONCLUSIONS: Radiotherapy was a potentially curative treatment with low toxicity in localised non-gastric MZL. Autoimmunity, H. pylori infection or both were detected in 60% of patients.

Caffeic acid and caffeine attenuate toxicity associated with malonic or methylmalonic acid exposure in Drosophila melanogaster.

The deficiency in the activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MCM, EC 5.4.99.2) leads to a condition called methylmalonic academia, which is characterised by the accumulation of methylmalonic (MMA), malonic (MA) or other organic acids. Importantly, we have recently found that supplementation with Ilex paraguariensis aqueous extract offered protection against toxicity associated with MMA or MA exposure to Drosophila melanogaster. Of note, caffeic acid (CA) and caffeine (CAF) were the major phytochemicals found in our Ilex paraguariensis crude extract. Therefore, here, we have exploited CA and/or CAF to test the hypothesis that supplementation with the isolated compounds (either alone or combined) could exert a protective effect against MMA or MA-induced toxicity in flies. Therefore, flies were exposed to MA (5 mM) or MMA (5 mM) and concomitantly treated with CA (1.39 µg/mL), CAF (1.27 µg/mL) or CA + CAF for 10 days for survival, and for 4 days for behavioural and biochemical assays. CA, CAF and CA + CAF treatments completely abolished the mortality associated with either MMA or MA exposure. Moreover, CA and CAF, either alone or combined, completely abolished behavioural changes, and completely protect against changes in thiobarbituric acid reactive substances (TBARS) levels, catalase (CAT) activity and MTT reduction ability, associated with MA or MMA exposure. In turn, CAF restored SOD activity in the head of flies exposed to MA or MMA. However, CA and CAF (either alone or combined) significantly decreased acetylcholinesterase (AChE) activity per se, while CAF alone protected from changes in AChE activity (in head tissue) associated with MA or MMA. Finally, CA and/or CAF were able to protect from a decrease in glucose and triglyceride levels associated with both MA and MMA exposures in haemolymph. Together, our data confirm the hypothesis that supplementation with CA and/or CAF offers protection against detrimental changes associated with MMA or MA exposure in flies, being responsible, at least in part, for the protective effect of I. paraguariensis crude extract which was reported previously.

A toxicological comparison between two uranium compounds in Artemia salina: Artificial seawater containing CaCO3.

Uranium (U) mining is an aquatic environmental concern because most of these harmful compounds are discharged into freshwater, reaching the saline environment as the final destination of this contaminated water. Carbonates are present in ocean waters and are essential for benthic organisms, however they may influence the U-induced toxicity. Thus, the aim of this study was to compare the toxicity of uranium nitrate (UN) and uranium acetate (UA) in Artemia salina (AS), which is one of the leading representatives of the marine biota. The cultures of AS (instar II) maintained in artificial seawater containing CaCO3 were exposed for 24 h to different concentrations of U compounds. The results showed that AS were more sensitive to UN (LC50 ≈ 15 µM) when compared with UA (LC50 ≈ 245 µM) indicating higher toxicity of this U compound. Calculated U speciation indicated that Ca2UO2(CO3)3 and (UO2)2CO3(OH)3- complexes predominated under our experimental conditions. The immobilization/lethality was observed after 9 h of exposure for both U compounds. However, only UN caused a significant decrease (≈40%) in the acetylcholinesterase (AChE) activity when compared with control. In order to observe preliminary toxicity effects, we evaluated oxidative stress parameters, such as catalase (CAT) activity, TBARS formation, radical species (RS) generation and cell membrane injury and/or apoptosis (CMI). In this study, we demonstrate that U compounds caused a significant decrease in CAT activity. Similarly, we also observed that UN increased TBARS levels in AS at concentrations 5 times lower than AU (10 µM and 50 µM, respectively). Furthermore, RS generation and CMI were enhanced only on AS treated with UN. Overall, the effects observed here were remarkably significant in AS exposed to UN when compared with AU. In this study, we showed different profiles of toxicity for both U compounds, contributing significantly to the current and scarce understanding of the aquatic ecotoxicity of this heavy metal.

Activation of SOD-3 is involved in the antioxidant effect of a new class of ß-aryl-chalcogenium azide compounds in Caenorhabditis elegans.

Organic selenium, tellurium and sulfur compounds have been studied due to their pharmacological properties. For instance, the ß-aryl-chalcogenium azide compounds have demonstrated antitumoral action in vitro. However, yet no pharmacological actions of this class of compounds were determined in vivo. Caenorhabditis elegans is a nematode that presents innumerable advantages in relation to mammalian models, such as having a small and transparent body, which allows the visualization of its internal anatomy, besides short life and low cost. Based on that, the aim of this work was to investigate the pharmacological and toxicological properties of ß-aryl-chalcogenium azide compounds in C. elegans. As well, to evaluate the capacity of organochalcogenium compounds to repair oxidative damage induced by hydrogen peroxide and the possible mechanism of action of these compounds using CF1553 transgenic strain with superoxide dismutase (SOD-3) tagged with GFP. Our results showed that ß-aryl-chalcogenium azide have low toxicity in wild-type worms and the pre-treatment protected against the damage induced by hydrogen peroxide at higher tested concentration. Associated with this, we observed that this protection is due in part to the increased expression of the antioxidant enzyme SOD-3. In conclusion, ß-aryl-chalcogenium azide compounds caused low toxicity and induced stress-resistance by modulating SOD-3 expression in C. elegans.

Survey of clinician opinions on the role of proton beam therapy in Australia and New Zealand.

INTRODUCTION: We surveyed the Australian and New Zealand (ANZ) radiation oncology community to assess their perceptions, understanding and experience of the current role of proton beam therapy (PBT) and the existing referral process to access PBT overseas, ahead of the development of the first PBT centre in Australia. METHODS: The survey was conducted between September and October 2019 using a 17-question instrument, which was distributed by email to all 632 radiation oncology fellows and trainees listed in the Royal Australian and New Zealand College of Radiologists database. RESULTS: One hundred and one respondents completed the survey, with an overall response rate of 16%. Most respondents were based in Australia (93%), with the majority working in public centres only (59%); 51% were > 10 years post fellowship and 17% were trainees. Most respondents (76%) reported moderate or high levels of confidence in the role of PBT. Only 28% had previously referred a patient for PBT overseas, with the most common referral indication being chordoma. Of those who had not previously referred a patient, 48% were not convinced about the rationale of PBT over current therapies available locally, 33% were not aware of the referral process, and 24% had concerns about the timeliness of a decision for government-funded PBT abroad. CONCLUSION: This survey has demonstrated that, although there is reasonable confidence in the role of PBT among ANZ radiation oncologists, there are a number of important aspects of PBT awareness, education and access that need to be developed prior to commencement of PBT in Australia.

Non-melanoma skin cancer in general practice: Radiotherapy is an effective treatment option.

BACKGROUND: Skin cancer is the most common malignancy that is managed in general practice, and non-melanoma skin cancer (NMSC) comprises the vast majority of presentations. Radiation therapy (RT) plays an important part in the management of NMSC and may be used as definitive treatment for low-risk cancers, as an adjuvant treatment for high-risk disease or alone for inoperable cases. OBJECTIVE: The aims of this article are to discuss: 1) types of RT; 2) role of RT, including its advantages and disadvantages; 3) side effects (toxicity) of RT; 4) outcomes from RT; 5) low- versus high-risk NMSCs and 6) some guidelines for general practitioners on when to refer patients for consideration of RT. DISCUSSION: The primary goal of treatment for NMSC is to cure the patient, and a secondary goal is to provide the best cosmetic and functional result with the minimum impact on quality of life. In deciding what modality of treatment to use, clinicians will need to take into account the site of the tumour, clinical stage, histological subtype and any high-risk features, patient comorbidities as well as patient preferences. RT provides a safe and effective alternative to surgery in select cases and is particularly useful for the elderly or where surgery might have a negative impact on function or cosmesis.

Dramatic radiotherapy response in a necrotic lymphoma mass: a case report.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) represents the most common form of non-Hodgkin lymphoma and is characterized by an aggressive natural history. It often presents with rapid symptom development and disease progression. Most lymphomas are inherently radiosensitive, which allows for effective disease control from relatively low radiation doses. We report a case of a dramatic radiotherapy response in a necrotic diffuse large B-cell lymphoma mass in an elderly patient with early-stage diffuse large B-cell lymphoma, illustrating the potential for palliative radiotherapy to reduce disease burden in patients not fit for systemic therapy. There is no current consensus recommendation for radiotherapy treatment in this setting. CASE PRESENTATION: A 97-year-old Caucasian woman presented to the emergency department of our institution with a painful, malodorous, necrotic right upper neck mass, which had progressed over a two-month period. Investigations confirmed stage 1A diffuse large B-cell lymphoma. Palliative radiotherapy was delivered to a dose of 25 Gray (Gy) in five fractions on alternate days over two consecutive weeks. After four months, the mass completely resolved with no residual symptoms. CONCLUSION: Dramatic responses resulting in durable local control and improvement in quality of life are achievable with palliative radiotherapy, owing to the radiosensitivity of diffuse large B-cell lymphoma.

Antidepressant-like effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in rats exposed to malathion: Involvement of BDNF-Trkß pathway and AChE.

BACKGROUND: Organophosphorus pesticides exert their toxic effects mainly by the inhibition of acetylcholinesterase (AChE), which is related to emotional disorders, such as depression. Atropine-oximes therapy is commonly used; however, the efficacy of oximes in the reactivation of AChE has been inconsistent. The objective of this study was to investigate the possible neuroprotective effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that combines the isatin and oxime functional groups, in rats exposed to malathion. The effect of Cℓ-HIN on the AChE activity and the BDNF-Trkß pathway in the prefrontal cortex of malathion-exposed rats were tested. METHODS: Wistar male rats were co-treated with Cℓ-HIN [50 mg/kg (p.o.) (3 mL/kg)] and/or malathion [250 mg/kg (i.p.) (5 mL/kg)] and performed behavioral tests twelve hours after these exposures. RESULTS: The Cℓ-HIN reversed the increased immobility time in the forced swimming test and the decreased grooming time in the splash test induced by malathion, but any significant difference was observed in locomotion analysis. These results demonstrate the antidepressant-like effect of Cℓ-HIN. The cortical AChE activity was reactivated by Cℓ-HIN in rats exposed to malathion. Malathion induced an increase in Trkß and a decrease in BDNF levels in the prefrontal cortex of rats, which were avoided by Cℓ-HIN. CONCLUSION: These findings support the hypothesis that Cℓ-HIN is an AChE reactivator with antidepressant-like properties, which is related to the improvement of BDNF-Trkß signaling after acute exposure to malathion in rats. Thus, the results allow suggesting the potential use of Cℓ-HIN as an oxime-based therapy against the neurotoxic effects of malathion.

Feedback survey on the Royal Australian and New Zealand College of Radiologists Faculty of Radiation Oncology trainee research requirement.

INTRODUCTION: The Royal Australian and New Zealand College of Radiologists Faculty of Radiation Oncology (FRO) requires trainees to complete a research project prior to the exit (phase II) examinations. We report results of a survey of current FRO trainees and Fellows graduating since 2013, regarding their experience of the overall requirement, supervision, barriers to project completion and subsequent publication. METHODS: A 32-question online survey was sent via email to 285 FRO members in July 2019. Responses were anonymous. RESULTS: The overall response rate was 32% (trainees 41%, Fellows 21%); 70% of respondents were trainees. About three-quarters of projects were retrospective reviews (64%) or surveys (13%), 94% met College requirements at first submission, 71% were published, and 81% were presented at a scientific meeting. Most assistance was provided by the project supervisor (57%), statistician (47%), another consultant (36%) or the Director of Training (28%). Finding time amongst other clinical/curriculum commitments, rotating to another training site and availability of a suitable supervisor were notable obstacles. Over half (52%) of respondents were satisfied/very satisfied with the process overall and 20% dissatisfied/very dissatisfied; 19% and 30%, respectively, thought requiring acceptance for peer review and completion prior to the phase II examination unreasonable/very unreasonable. Four per cent reported being less likely to be involved in future research as a result of this experience. CONCLUSION: While the majority of respondents perceive the FRO research requirements as reasonable, a significant minority are not satisfied with aspects of the programme. Amendment of the pre-phase II stipulation may be worthy of consideration.