[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

Survey of brachytherapy training experience among radiation oncology trainees and fellows in the Royal Australian and New Zealand College of Radiologists (RANZCR).

INTRODUCTION: To evaluate brachytherapy training experience among trainees and fellows trained through the Royal Australian and New Zealand College of Radiologists (RANZCR). METHODS: All current trainees and fellows (who obtained fellowship from 2015 onwards) were sent an online anonymous questionnaire on various aspects of brachytherapy training, including number of cases observed/ performed, opinions on brachytherapy assessment during training, barriers to brachytherapy training and future role of brachytherapy. RESULTS: The overall survey response rate was 24% (40/161 trainees, 30/126 fellows). Of the 70 respondents, 50 (71%), 38 (54%) and 43 (61%) reported to have received formal brachytherapy teaching from radiation oncologists, radiation therapists and medical physicists respectively. Most respondents had exposure to gynaecology brachytherapy - two-thirds of trainees and all fellows have performed at least one gynaecology brachytherapy procedure. Prostate brachytherapy exposure was more limited - by the end of training, 27% and 13% of fellows did not have exposure to LDR and HDR prostate brachytherapy. More than two-thirds indicated there should be a minimum number of brachytherapy case requirements during training, and half indicated that trainees should be involved in ≥6 gynaecology brachytherapy procedures. Barriers affecting training include lack of caseload (70%) and perceived decreasing role of brachytherapy (66%). Forty-three percent of respondents were concerned about the decline in brachytherapy utilisation. CONCLUSION: This is the first survey on brachytherapy training experience among RANZCR trainees and fellows. It highlighted limited brachytherapy exposure during RANZCR training, and the need to revisit brachytherapy training requirement in the current training programme, along with long-term brachytherapy workforce planning.

The use of collimator angle optimization and jaw tracking for VMAT-based single-isocenter multiple-target stereotactic radiosurgery for up to six targets in the Varian Eclipse treatment planning system.

PURPOSE: Island blocking occurs in single-isocenter multiple-target (SIMT) stereotactic radiotherapy (SRS) whenever targets share multi-leaf collimator (MLC) leaf pairs. This study investigated the effect on plan quality and delivery, of reducing island blocking through collimator angle optimization (CAO). In addition, the effect of jaw tracking in this context was also investigated. METHODS: For CAO, an algorithm was created that selects the collimator angle resulting in the lowest level of island blocking, for each beam in any given plan. Then, four volume-modulated arc therapy (VMAT) SIMT SRS plans each were generated for 10 retrospective patients: two CAO plans, with and without jaw tracking, and two plans with manually selected collimator angles, with and without jaw tracking. Plans were then assessed and compared using typical quality assurance procedures. RESULTS: There were no substantial differences between plans with and without CAO. Jaw tracking produced statistically significant reduction in low-dose level parameters; healthy brain V10% and mean dose were reduced by 9.66% and 15.58%, respectively. However, quantitative values (108 cc for V10% and 0.35 Gy for mean dose) were relatively small in relation to clinical relevance. Though there were no statistically significant changes in plan deliverability, there was a notable trend of plans with jaw tracking having lower gamma analysis pass rates. CONCLUSION: These findings suggest that CAO has limited benefit in VMAT SIMT SRS of 2-6 targets when using a low-dose penalty to the healthy brain during plan optimization in Eclipse. As clinical benefits of jaw tracking were found to be minimal and plan deliverability was potentially reduced, a cautious approach would be to exclude jaw tracking in SIMT SRS plans.

Comparison of TG43 and Hounsfield Unit-based TG186 brachytherapy dose metrics in Oncentra Brachy for 100 patients receiving interstitial partial breast irradiation.

PURPOSE: The aim of the study was to conduct a retrospective analysis of 100 patients who received interstitial accelerated partial breast irradiation at a single institution, comparing the standard American Association of Physicists in Medicine Task Group (TG) 43 dose calculation algorithm to the model-based dose calculation algorithms (MBDCAs) available in the Oncentra Brachy treatment planning system. METHODS AND MATERIALS: Dose-volume histogram parameters were compared between the different dose calculation algorithms for the planning target volume and organs at risk. and a statistical analysis was performed. The resulting changes in isodose distribution were assessed, with the worst-case data presented. RESULTS: The TG43 algorithm calculated higher doses to all structures compared with the MBDCAs. The largest discrepancy was observed for the skin, with maximum doses on average 2.0% lower with the MBDCA. The newly released Hounsfield Unit-based algorithm further decreased the skin dose compared with TG43 by <0.5%. CONCLUSIONS: This study demonstrates that the differences between TG43 and MBDCA as implemented in Oncentra Brachy for accelerated partial breast irradiation are clinically insignificant in the treatment area and nearby organs at risk. Justification for investing in MBDCAs for this treatment site is limited when considering the additional calculation time, introduced uncertainties, and cost.

A Clinician's Guide to Cancer-Derived Exosomes: Immune Interactions and Therapeutic Implications.

Understanding of the role of immunity in the regulation of cancer growth continues to rapidly increase. This is fuelled by the impressive results yielded in recent years by immune checkpoint inhibitors, which block regulatory pathways to increase immune-mediated cancer destruction. Exosomes are cell-secreted membranous nanoscale vesicles that play important roles in regulating physiological and pathophysiological processes. Cancer-derived exosomes (CDEXs) and their biologically-active cargos have been proven to have varied effects in malignant progression, including the promotion of angiogenesis, metastasis, and favorable microenvironment modification. More recently, there is an increasing appreciation of their role in immune evasion. In addition to CDEXs, there are immune-derived exosomes that facilitate communication between immune cells in the non-malignant setting. Investigation of cancer-mediated mechanisms behind interruption or modification of these normal exosomal pathways may provide further understanding of how malignant immune evasion is accomplished. Accumulating evidence indicates that immune-active CDEXs also have the potential to impact clinical oncological management. Whilst immune checkpoint inhibitors have well-established pharmacologically-targeted pathways involving the immune system, other widely used treatments such as radiation and cytotoxic chemotherapies do not. Thus, investigating exosomes in immunotherapy is important for the development of next-generation combination therapies. In this article, we review the ways in which CDEXs impact individual immune cell types and how this contributes to the development of immune evasion. We discuss the relevance of lymphocytes and myeloid-lineage cells in the control of malignancy. In addition, we highlight the ways that CDEXs and their immune effects can impact current cancer therapies and the resulting clinical implications.

Towards real time in-vivo rectal dosimetry during trans-rectal ultrasound based high dose rate prostate brachytherapy using MOSkin dosimeters.

PURPOSE: To compare the dose measured by MOSkin dosimeters coupled to a trans-rectal ultrasound (TRUS) probe to the dose predicted by the brachytherapy treatment planning system (BTPS) during high dose rate (HDR) prostate brachytherapy (pBT), and to examine the feasibility of performing real-time catheter-by-catheter analysis of in-vivo rectal dosimetry during TRUS based HDR pBT. METHOD: Four MOSkin dosimeters were coupled to a TRUS probe during 20 TRUS-based HDR pBT treatment fractions. The measured MOSkin doses were retrospectively compared to those predicted by the BTPS for the total treatment fraction, as well as on a per catheter basis. RESULTS: The average relative percentage difference between MOSkin measured and BTPS predicted doses for a total treatment fraction was 0.3% ± 11.6% (k = 1), with a maximum of 23.2% and a minimum of -29.0%. The average relative percentage difference per catheter was +2.5% ± 16.9% (k = 1). The majority (64%) of per catheter MOSkin measured doses agreed with the treatment planning system within the calculated uncertainty budget of 12.3%. CONCLUSION: The results of the study agreed well with previously published data, despite differences in clinical workflows. To improve the redundancy to potential dosimeter errors, a minimum of 4 MOSkin dosimeters should be used when performing real-time in-vivo rectal dosimetry for HDR pBT, and error thresholds should be based off the total combined uncertainty estimate of measurement. 'Real time' error thresholds can be more confidently applied in the future through enhanced integration between IVD systems with both the imaging device and the BTPS/afterloader.

Endobronchial brachytherapy in the management of lung malignancies: 20 years of experience in an Australian center.

OBJECTIVES: Management of end-stage lung cancers focuses on symptom control, requiring multimodality management. Endobronchial brachytherapy (EBB) is an evidence-based approach allowing safe delivery of clinically meaningful radiation doses. We provide a summary of treatment characteristics and clinical outcomes of EBB in a single center. METHODS AND MATERIALS: Our retrospective study examined all EBB procedures performed at St George Hospital, NSW, Australia, between 1997 and 2016. Patients received single-fraction brachytherapy treatment under procedural sedation, using either the pulsed-dose-rate or high dose-rate modality. Symptomatic response was noted at the 4- to 6-week followup consultation. RESULTS: Ninety-two EBB procedures were identified in 83 patients, with 75 patients treated with pulsed-dose-rate and 17 with high-dose-rate. Clinical and/or radiological airway obstruction in a prior high-dose irradiated volume was the most common indication for treatment (85%). Sixty (72%) patients had a partial or complete response of symptoms. Patients with hemoptysis were more likely to respond than those with airway obstruction (92% vs. 70%; p = 0.036). There was no difference in clinical response between pulsed-dose-rate and high-dose-rate patients (p = 0.24). Median overall survival was 8 months, with a statistically significant difference in those with clinical response (4 vs. 9 months; p = 0.0101). No Grade >2 toxicities were recorded. CONCLUSIONS: We present the largest Australian series of EBB to date. We continue to demonstrate that despite a variety of symptomatic presentations and histologies, EBB is an effective approach to the palliation of malignant lung lesions. Given its low risk of toxicity, EBB is recommended as an option in the palliative treatment of endobronchial malignancies.

A risk-based approach to development of ultrasound-based high-dose-rate prostate brachytherapy quality management.

PURPOSE: The purpose of this study was to apply a risk-based approach to the development of a quality management (QM) program for ultrasound-based high-dose-rate (HDR) prostate brachytherapy (pBT) treatment planning and delivery. METHODS AND MATERIALS: A QM program was developed by a multidisciplinary team, using both an in-house risk-and-benefit balance impact template (RABBIT) tool and a failure modes and effect analysis (FMEA). FMEA scores were determined by three physicists, one radiation therapist and two radiation oncologists who were familiar with the protocol. The QM program produced by both risk-based techniques was then compared and consolidated. RESULTS: The RABBIT tool identified 26 potential risks during the treatment planning and delivery process. During the FMEA, a total of 35 potential failure modes were identified from the seven major processes in ultrasound-based HDR pBT. For the 35 potential failure modes, risk priority number scores ranged from 14 to 267. The highest ranked failure mode was identified to be mislabeling/connection of the transfer tubes/catheters. From the risks analyses, a comprehensive QM program was developed. CONCLUSION: Both the RABBIT tool and process mapping and FMEA were shown to be valuable tools in developing a QM program for ultrasound-based HDR pBT treatments. A considerable number of the potential failure modes identified in both tools were related to human or procedural errors, highlighting the importance of checklists and protocols in delivering a safe and effective ultrasound-based HDR pBT treatment.

Dose accumulation of multiple high dose rate prostate brachytherapy treatments in two commercially available image registration systems.

PURPOSE: The purpose of this study was to assess whether deformable image registration (DIR) is required for dose accumulation of multiple high dose rate prostate brachytherapy (HDRPBT) plans treated with the same catheter pattern on two different CT datasets. METHOD: DIR was applied to 20 HDRPBT patients' planning CT images who received two treatment fractions on sequential days, on two different CT datasets, with the same implant. Quality of DIR in Velocity and MIM image registration systems was assessed by calculating the Dice Similarity Coefficient (DSC) and mean distance to agreement (MDA) for the prostate, urethra and rectum contours. Accumulated doses from each system were then calculated using the same DIR technique and dose volume histogram (DVH) parameters compared to manual addition with no DIR. RESULTS: The average DSC was found to be 0.83 (Velocity) and 0.84 (MIM), 0.80 (Velocity) and 0.80 (MIM), 0.80 (Velocity) and 0.81 (MIM), for the prostate, rectum and urethra contours, respectively. The average difference in calculated DVH parameters between the two systems using dose accumulation was less than 1%, and there was no statistically significant difference found between deformably accumulated doses in the two systems versus manual DVH addition with no DIR. CONCLUSION: Contour propagation using DIR in velocity and MIM was shown to be at least equivalent to inter-observer contouring variability on CT. The results also indicate that dose accumulation through manual addition of DVH parameters may be sufficient for HDRPBT treatments treated with the same catheter pattern on two different CT datasets.

High-dose-rate brachytherapy boost for prostate cancer: Outcomes and genitourinary toxicity.

AIMS: To report disease outcomes and late urinary toxicity profile. To assess the impact of changing technique and evolving quality assurance on genitourinary toxicity rates. METHODS AND MATERIALS: One hundred eighty patients were treated with external beam radiation therapy and high-dose-rate brachytherapy (HDRB) for localized intermediate- and high-risk prostate cancer, between December 2002 and February 2012. The HDRB technique evolved over the period of this study, from 19.5 Gy/3 (n = 68), to 17 Gy/2 (n = 40), 18 Gy/2 (n = 39), and most recently 19 Gy/2 (n = 33). In the two fraction cohort, 68 patients underwent additional correction for catheter displacement before each fraction. RESULTS: With a median followup of 5.2 years, 5-year freedom from failure was 93.7% for intermediate, and 76.0% for high risk patients. The 3- and 6-year cumulative stricture incidence for all patients was 7.8% and 15.3%, respectively. There was no statistically significant difference in stricture rate for the four dose levels used nor between the three fractions and the two fraction technique overall. The 19 Gy/2 fractionation group had the lowest 3-year stricture rate (3.0%). The addition of correction for intrafraction catheter displacement did not result in a statistically significant difference in stricture rates, although the severity of strictures has been reduced. CONCLUSIONS: Our biochemical control is consistent with other similar series. We found no increase in late urinary toxicity with a two fraction, two implant HDRB technique compared with three fractions. The HDRB dose did not correlate with stricture rates in our series. Correction of intra-fraction catheter displacement did not lead to a statistically significant reduction in stricture rates, although may have mitigated the effects of dose escalation.

Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution.

INTRODUCTION: We aim to report the outcome of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiotherapy with or without chemotherapy at a single Australian institution. METHOD: Between July 2004 and March 2013, 53 patients were referred for radiation treatment following EPP, of whom 49 were suitable for adjuvant treatment. Radiation treatment initially involved a 3D conformal, mixed electron/photon technique, delivering 45-50.4 Gy in 25-28 fractions (31 patients) and subsequently a nine-field intensity-modulated radiotherapy technique, delivering 50.4-54 Gy in 28-30 fractions (18 patients). Fifty-five per cent of patients also received pre-operative chemotherapy. We assessed toxicity, disease-specific and overall survival in patients who commenced radiation treatment. RESULTS: Forty-one patients (84%) completed treatment as prescribed. Six patients stopped prematurely due to toxicity, and two with disease progression. Most patients discontinuing due to toxicity received over 90% of the prescribed dose. Common acute toxicities included nausea, fatigue, anorexia and dermatitis. Severe early toxicities were rare. Late toxicities were uncommon, with the exception of a persistent elevation in liver enzymes in those with right-sided disease. Neither clinical hepatitis nor radiation pneumonitis was documented. With a median follow up of 18.7 months, median disease-free and overall survival were 21.6 and 30.5 months, respectively, and 2-year overall survival was 57.3%. CONCLUSION: Hemithoracic radiotherapy following EPP, although associated with significant early toxicity, is well tolerated. Most patients complete the prescribed treatment, and clinically significant late toxicities are rare.

Corneal optics after reading, microscopy and computer work.

PURPOSE: To compare lid-induced changes in corneal optics following reading, microscopy and computer work. METHODS: Nine subjects with normal ocular health were recruited for the study. Five subjects were myopic, two were emmetropic, one was astigmatic and one was hyperopic. Corneal topography was measured before and after 60 mins of reading a novel, performing a blood cell counting task on a microscope and Internet searching. Corneal topography data were used to derive the corneal wavefront Zernike coefficients up to the fourth order. A meridian analysis of instantaneous corneal power along the upper 90-degree semi-meridian was performed to examine local changes caused by eyelid pressure. Digital photography was used to capture body posture and eyelid position during the tasks. RESULTS: Each of the three tasks showed systematically different effects on both the characteristics and location of corneal topography changes. Reading and microscopy generally exhibited larger and more centrally located changes compared with the computer task. Differences in wavefront aberration characteristics between the three tasks were apparent in both lower and higher order aberrations. The location of corneal distortions differed significantly between microscopy and computer work, with microscopy causing distortions to occur closer to the videokeratoscope measurement axis compared with computer work (p = 0.015). CONCLUSIONS: Reading, microscopy and computer work have different effects on corneal aberrations. The results are in agreement with the hypothesis that lid-induced corneal aberrations may play a role in myopia development.