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Cancer systemic therapeutics and radiotherapy are often associated with dermatological toxicities that may reduce patients' quality of life and impact their course of cancer treatment. These toxicities cover a wide range of conditions that can be complex to manage with increasing severity. This review provides details on twelve common dermatological toxicities encountered during cancer treatment and offers measures for their prevention and management, particularly in the Australian/New Zealand context where skincare requirements may differ to other regions due to higher cumulative sun damage caused by high ambient ultraviolet (UV) light exposure. Given the frequency of these dermatological toxicities, a proactive phase is envisaged where patients can actively try to prevent skin toxicities.

Purpose: We aimed to compare Australian health system costs at 12 months for adjuvant whole-brain radiotherapy (WBRT) treatment after stereotactic radiosurgery (SRS) and/or surgery versus observation among adults with one to three melanoma brain metastases. We hypothesized that treatment with adjuvant WBRT and subsequent healthcare would be more expensive than SRS/surgery alone., Methods: The analysis was conducted alongside a multicentre, randomized phase III trial. A bespoke cost questionnaire was used to measure healthcare use, including hospitalizations, specialist and primary care visits, imaging, and medicines over 12 months. Mean per-patient costs were calculated based on the quantity of resources used and unit costs, reported in Australian dollars ($AU), year 2018 values. Skewness of cost data was determined using normality tests and censor-adjusted costs reported using the Kaplan-Meier sample average method. The analysis of difference in mean costs at each 2-month time point and at 12 months was performed and checked using Kruskal-Wallis, generalized linear models with gamma distribution and log link, modified Park test, ordinary least squares, and non-parametric bootstrapping., Results: In total, 89 patients with similar characteristics at baseline were included in the cost analysis (n = 43 WBRT; n = 46 observation). Hospitalization cost was the main cost, ranging from 63 to 89% of total healthcare costs. The unadjusted 12-monthly cost for WBRT was $AU71,138 ± standard deviation 41,475 and for observation $AU69,848 ± 33,233; p = 0.7426. The censor-adjusted 12-monthly cost for WBRT was $AU90,277 ± 36,274 and $AU82,080 ± 34,411 for observation. There was no significant difference in 2-monthly costs between groups (p > 0.30 for all models)., Conclusions: Most costs were related to inpatient hospitalizations associated with disease recurrence. Adding WBRT after local SRS/surgery for patients with one to three melanoma brain metastases did not significantly increase health system costs during the first 12 months., Trial Registration: ACTRN12607000512426, prospectively registered 14 September 2007., (© 2022. The Author(s).)

Background: Melanoma brain metastases (MBM) often cause morbidity and mortality for stage IV melanoma patients. An ongoing randomised phase III trial (NCT01503827 - WBRT-Mel) evaluates the role of adjuvant whole brain radiotherapy (WBRT) following local treatment of MBM. Hippocampal avoidance during WBRT (HA-WBRT) has shown memory and neurocognitive function (NCF) preservation in the RTOG-0933 phase II study. This study assessed the quality assurance of HA-WBRT within the WBRT-Mel trial according to RTOG-0933 study criteria., Methods: Hippocampal avoidance was allowed in approved centres with intensity-modulated radiotherapy capability. Patients treated by HA-WBRT were not randomized within the WBRT arm. The RTOG 0933 contouring Atlas was used to contour hippocampi. In the trial co-ordinating centre, patients were treated with volumetric modulated arc therapy using complementary arcs; similar techniques were used at other sites. Dosimetric data were extracted retrospectively and analysed in accordance with RTOG 0933 study constraints criteria., Results: Among the 215 patients accrued to the WBRT-Mel study between April 2009 and September 2017, 107 were randomized to the WBRT arm, 22 were treated by HA-WBRT in 4 centers. Eighteen patients were treated in the same centre. The median age was 65 years. The commonest (91%) HA-WBRT schema was 30 Gy in 10 fractions. Prior to HA-WBRT, 10 patients had been treated by surgery alone, six by radiosurgery alone, four by surgery and radiosurgery and two exclusively by simultaneous integrated boost concurrent to HA-WBRT. Twenty patients were treated with intention to spare both hippocampi and two patients had MBM close to one hippocampus and were treated with intention to spare the contralateral hippocampus. According to RTOG-0933 study criteria, 18 patients (82%) were treated within constraints and four patients (18%) had unacceptable deviation in just one hippocampus., Conclusions: This dosimetric quality assurance study shows good compliance (82%) according to RTOG-0933 study dosimetric constraints. Indeed, all patients respected RTOG hippocampal avoidance constraints on at least one hippocampus. In the futureanalysis of the WBRT-Mel trial, the NCF of patients on the observation arm, WBRT arm and with HA-WBRT arm will be compared.

68 Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% ( n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% ( n = 71/99). Forty-five percent ( n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% ( n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% ( n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% ( n = 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Unlabelled: In prostate cancer with biochemical failure after therapy, current imaging techniques have a low detection rate at the prostate-specific antigen (PSA) levels at which targeted salvage therapy is effective. (11)C-choline and (18)F-fluoromethylcholine, though widely used, have poor sensitivity at low PSA levels. (68)Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga-N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid]) has shown promising results in retrospective trials. Our aim was to prospectively compare the detection rates of (68)Ga-PSMA versus (18)F-fluoromethylcholine PET/CT in men who were initially managed with radical prostatectomy, radiation treatment, or both and were being considered for targeted therapy., Methods: A sample of men with a rising PSA level after treatment, eligible for targeted treatment, was prospectively included. Patients on systemic treatment were excluded. (68)Ga-PSMA, (18)F-fluoromethylcholine PET/CT, and diagnostic CT were performed sequentially on all patients between January and April 2015, and the images were assessed by masked, experienced interpreters. The findings and their impact on management were documented, together with the results of histologic follow-up when feasible., Results: In total, 38 patients were enrolled. Of these, 34 (89%) had undergone radical prostatectomy and 4 (11%) had undergone radiation treatment. Twelve (32%) had undergone salvage radiation treatment after primary radical prostatectomy. The mean PSA level was 1.74 ± 2.54 ng/mL. The scan results were positive in 26 patients (68%) and negative with both tracers in 12 patients (32%). Of the 26 positive scans, 14 (54%) were positive with (68)Ga-PSMA alone, 11 (42%) with both (18)F-fluoromethylcholine and (68)Ga-PSMA, and only 1 (4%) with (18)F-fluoromethylcholine alone. When PSA was below 0.5 ng/mL, the detection rate was 50% for (68)Ga-PSMA versus 12.5% for (18)F-fluoromethylcholine. When PSA was 0.5-2.0 ng/mL, the detection rate was 69% for (68)Ga-PSMA versus 31% for (18)F-fluoromethylcholine, and when PSA was above 2.0, the detection rate was 86% for (68)Ga-PSMA versus 57% for (18)F-fluoromethylcholine. On lesion-based analysis, (68)Ga-PSMA detected more lesions than (18)F-fluoromethylcholine (59 vs. 29, P < 0.001). The tumor-to-background ratio in positive scans was higher for (68)Ga-PSMA than for (18)F-fluoromethylcholine (28.6 for (68)Ga-PSMA vs. 9.4 for (18)F-fluoromethylcholine, P < 0.001). There was a 63% (24/38 patients) management impact, with 54% (13/24 patients) being due to (68)Ga-PSMA imaging alone. Histologic follow-up was available for 9 of 38 patients (24%), and 9 of 9 (68)Ga-PSMA-positive lesions were consistent with prostate cancer ((68)Ga-PSMA was true-positive). The lesion positive on (18)F-fluoromethylcholine imaging and negative on (68)Ga-PSMA imaging was shown at biopsy to be a false-positive (18)F-fluoromethylcholine finding ((68)Ga-PSMA was true-negative)., Conclusion: In patients with biochemical failure and a low PSA level, (68)Ga-PSMA demonstrated a significantly higher detection rate than (18)F-fluoromethylcholine and a high overall impact on management., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Treatment of pelvic lymph nodes (PLNs) in higher risk prostate carcinoma is controversial. The primary focus of the study was to evaluate the early toxicity profile for this cohort of patients treated with Volumetric Modulated Arc Therapy (VMAT)., Methods: Patient, tumour, and treatment characteristics of those who received VMAT from May 2010 to December 2012 were analysed. A simplified contouring process of the PLNs to the aortic bifurcation was developed based on consensus guidelines. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were documented according to the Radiation Therapy Oncology Group (RTOG) Version 2 Guidelines. Successive Prostate Specific Antigen (PSA) values after treatment were measured on average 3 months apart., Results: 113 patients were treated between May 2010 to December 2012 with a median follow-up of 14 months. No patients experienced acute grade 3 or 4 GU and GI toxicity. Only 1 patient experienced a late grade 3 GU complication. No late grade 4 GU or GI events have yet occurred., Conclusions: This study reviews the first Australian experience of VMAT in the treatment of pelvic lymph nodes in prostate cancer, specifically to the level of the aortic bifurcation. It demonstrates a favorable acute toxicity profile whilst treating large PLN volumes with optimal dose coverage.

Four cases previously treated with ipilimumab with a total of six histologically confirmed symptomatic lesions of RNB without any sign of active tumour following stereotactic irradiation of MBM are reported. These lesions were all originally thought to be disease recurrence. In two cases, ipilimumab was given prior to SRT; in the other two ipilimumab was given after SRT. The average time from first ipilimumab to RNB was 15 months. The average time from SRT to RNB was 11 months. The average time from first diagnosis of MBM to last follow-up was 20 months at which time three patients were still alive, one with no evidence of disease. These cases represent approximately three percent of the total cases of melanoma and ten percent of those cases treated with ipilimumab irradiated in our respective centres collectively. We report this to highlight this new problem so that others may have a high index of suspicion, allowing, if clinically warranted, aggressive surgical salvage, possibly resulting in increased survival. Further studies prospectively collecting data to understand the denominator of this problem are needed to determine whether this problem is just the result of longer survival or whether there is some synergy between these two modalities that are increasingly being used together.

Objective: The study was designed to examine whether the availability of reduced-processing decision support system interfaces could improve the decision making of inexperienced personnel in the context of, Background: Although research into reduced-processing decision support systems has demonstrated benefits in minimizing cognitive load, these benefits have not typically translated into direct improvements in decision accuracy because of the tendency for inexperienced personnel to focus on less-critical information. The authors investigated whether reduced-processing interfaces that direct users' attention toward the most critical cues for decision making can produce improvements in decision-making performance., Method: Novice participants made incident command-related decisions in experimental conditions that differed according to the amount of information that was available within the interface, the level of control that they could exert over the presentation of information, and whether they had received decision training., Results: The results revealed that despite receiving training, participants improved in decision accuracy only when they were provided with an interface that restricted information access to the most critical cues., Conclusion: It was concluded that an interface that restricts information access to only the most critical cues in the scenario can facilitate improvements in decision performance., Application: Decision support system interfaces that encourage the processing of the most critical cues have the potential to improve the accuracy and timeliness of decisions made by inexperienced personnel.

Purpose: Volumetric modulated arc therapy (VMAT) can deliver intensity modulated radiotherapy (IMRT) like dose distributions in a short time; this allows the expansion of IMRT treatments to palliative situations like brain metastases (BMs). VMAT can deliver whole brain radiotherapy (WBRT) with hippocampal avoidance and a simultaneous integrated boost (SIB) to achieve stereotactic radiotherapy (SRT) for BMs. This study is an audit of our experience in the treatment of brain metastases with VMAT in our institution., Methods and Materials: Metastases were volumetrically contoured on fused diagnostic gadolinium enhanced T1 weighted MRI/planning CT images. Risk organs included hippocampus, optic nerve, optic chiasm, eye, and brain stem. The hippocampi were contoured manually as one paired organ with assistance from a neuroradiologist. WBRT and SIB were integrated into a single plan., Results: Thirty patients with 73 BMs were treated between March 2010 and February 2012 with VMAT. Mean follow up time was 3.5 months. For 26 patients, BMs arose from primary melanoma and for the remaining four patients from non-small cell lung cancer (n= 2), primary breast cancer, and sarcoma. Mean age was 60 years. The male to female ratio was 2:1. Five patients were treated without hippocampal avoidance (HA) intent. The median WBRT dose was 31 Gy with a median SIB dose for BMs of 50 Gy, given over a median of 15 fractions. Mean values for BMs were as follows: GTV = 6.9 cc, PTV = 13.3 cc, conformity index = 8.6, homogeneity index = 1.06. Mean and maximum hippocampus dose was 20.4 Gy, and 32.4 Gy, respectively, in patients treated with HA intent. Mean VMAT treatment time from beam on to beam off for one fraction was 3.43 minutes, which compared to WBRT time of 1.3 minutes. Twenty out of 25 assessable lesions at the time of analysis were controlled. Treatment was well tolerated; grade 4 toxicity was reported in one patient. The median overall survival was 9.40 months, Conclusions: VMAT for BMs is feasible, safe and associated with a similar survival times and toxicities to conventional SRT+/-WBRT. The advantage of VMAT is that WBRT and SRT can be delivered at the same time on one machine.

Brain metastasis is common in patients with melanoma and represents a significant cause of morbidity and mortality. There have been no specific randomized trials for patients with melanoma brain metastasis, so treatment is based on management of brain metastasis in general and requires multidisciplinary expertise including radiation oncology, neurosurgery, medical oncology, and palliative care. In this paper, we summarize the prognosis, general management, and the role of radiation therapy in the management of metastatic melanoma in the brain.

Radiotherapy (RT) can cause haemostasis in select cases of malignant bleeding. We present two cases where RT was used to prevent fatal exsanguination from bleeding skin malignancies. Treatment was with radical intent in one case and palliative intent in the other. The dose used in both cases was 20 Gray (Gy) in 5 fractions. To our knowledge, this is the first report of radiation-induced haemostasis in bleeding skin malignancies.

Background: Cerebral metastases are a common cause of death in patients with melanoma. Systemic drug treatment of these metastases is rarely effective, and where possible surgical resection and/or stereotactic radiosurgery (SRS) are the preferred treatment options. Treatment with adjuvant whole brain radiotherapy (WBRT) following neurosurgery and/or SRS is controversial. Proponents of WBRT report prolongation of intracranial control with reduced neurological events and better palliation. Opponents state melanoma is radioresistant; that WBRT yields no survival benefit and may impair neurocognitive function. These opinions are based largely on studies in other tumour types in which assessment of neurocognitive function has been incomplete., Methods/design: This trial is an international, prospective multi-centre, open-label, phase III randomised controlled trial comparing WBRT to observation following local treatment of intracranial melanoma metastases with surgery and/or SRS. Patients aged 18 years or older with 1-3 brain metastases excised and/or stereotactically irradiated and an ECOG status of 0-2 are eligible. Patients with leptomeningeal disease, or who have had previous WBRT or localised treatment for brain metastases are ineligible. WBRT prescription is at least 30 Gy in 10 fractions commenced within 8 weeks of surgery and/or SRS. Randomisation is stratified by the number of cerebral metastases, presence or absence of extracranial disease, treatment centre, sex, radiotherapy dose and patient age. The primary endpoint is the proportion of patients with distant intracranial failure as determined by MRI assessment at 12 months. Secondary end points include: survival, quality of life, performance status and neurocognitive function., Discussion: Accrual to previous trials for patients with brain metastases has been difficult, mainly due to referral bias for or against WBRT. This trial should provide the evidence that is currently lacking in treatment decision-making for patients with melanoma brain metastases. The trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG-study 01-07), and the Trans Tasman Radiation Oncology Group (TROG) but international participation is encouraged. Twelve sites are open to date with 43 patients randomised as of the 31st March 2011. The target accrual is 200 patients., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000512426.