An evaluation of the use and efficacy of behavioural therapy when treating paediatric patients with radiation therapy.

INTRODUCTION: The paediatric radiation therapy group (PRTG) provided a multidisciplinary network to support patients accessing radiation therapy (RT). This study aims to evaluate the use and efficacy of behaviour therapy practices used by the PRTG. METHODS: A retrospective cross-sectional review of general anaesthetic (GA) utilisation for paediatric patients was completed between 1 January 2010 and 30 June 2014. The PRTG incorporated behavioural therapy techniques into all appointments but offered additional play appointments to children unable to comply with the requirements of RT. This aimed to increase their compliance and minimise GA use. RESULTS: Two-hundred and seventy-four patients had 5402 occasions of service, of which 1361 were delivered under GA (25.2%). Two-hundred and fifty-seven patients met the eligibility criteria. Patients under 8 years who required GA for their entire treatment reduced for each year of increase in age (odds ratio 0.37, 95% confidence interval 0.27-0.51, P < 0.001). Participants 3 years and younger were shown not as likely to change their GA requirements with the use of play appointments. Seventy-eight per cent (83/106) of 3-8-year-olds used no GA or ceased GA during treatment. CONCLUSIONS: Most paediatric patients <3 years will gain minimal benefit to reduce GA use from additional play appointments. Children older than nine were not likely to require play appointments to be compliant with RT. Encouragingly, 53.3% of 3-8-year-olds who were categorised as full GA after CT planning did not continue to a full course of GA due to the behavioural therapy interventions of the PRTG.

Modified volumetric modulated arc therapy technique with reduced planning and treatment time for craniospinal irradiation utilising two isocentres.

INTRODUCTION: Paediatric patients (individuals below 18 years of age) requiring cranial-spinal irradiation (CSI) at our institution are commonly planned and treated using a three isocentre (3-ISO) volumetric modulated arc therapy (VMAT) technique. A modified two isocentre (2-ISO) VMAT technique was investigated with the aim to improve workflow and reduce planning and treatment time. METHODS: Five CSI paediatric patients previously treated with a 3-ISO VMAT technique were retrospectively replanned using a 2-ISO VMAT technique. The 2-ISO VMAT plans were reviewed and approved by a radiation oncologist (RO) before undergoing patient-specific quality assurance (QA) procedures, performed by a radiation oncology medical physicist (ROMP). Planning target volume (PTV) coverage, organ-at-risk (OAR) dose as well as planning and treatment durations of the first five patients utilising 2-ISO technique were compared with 3-ISO technique. RESULTS: The average percentage difference in PTV coverage by 95% reference dose between the 2-ISO and 3-ISO is 0.14%, and the average difference in OAR median dose is 0.68 Gy. Conformity and homogeneity indices have the same averages at 1.18 and 0.4 respectively. Patient-specific physics QA results were all comparable with the 3-ISO averages at 98.84% and the 2-ISO at 98.71%. Planning duration for the 2-ISO was reduced by up to 75%, and daily treatment duration was reduced by up to 50%. Of all the previously treated CSI patients using a 3-ISO technique, 45% were suitable for the 2-ISO technique. CONCLUSION: The 2-ISO VMAT technique provided comparable dose distribution based on PTV coverage, OAR dose and plan metric indices. Reduced planning and treatment duration with the 2-ISO technique facilitated improved workflow with decreased sedation time for paediatric patients requiring a general anaesthesia.

Management trends and outcomes of pineal germinoma in a multi-institutional Australian cohort.

Pineal germinoma is rare with high cure rates following craniospinal radiotherapy. Efforts to reduce the radiotherapy dose and field via combination with chemotherapy suggest comparable disease control and reduced neurocognitive impairments, while the efficacy of immunotherapy in pineal germinoma remains undetermined. This report aimed to review clinical outcomes in patients treated for pineal germinoma in Queensland, Australia, and assess for Programmed Death-Ligand1 (PD-L1) expression. Patients who commenced radiation and/or chemotherapy for pineal germinoma from 2005 to 2017 were retrospectively identified using Queensland Oncology Online database. Demographic, diagnostic, treatment, and outcome data was obtained from electronic medical records. PD-L1 immuno-histochemistry was performed on available specimens. Eighteen patients with long-term follow-up data were identified. Median age at diagnosis was 16.8 years (range 9-46 years). Diagnosis was made histologically in fifteen patients, and radiologically in three. All patients underwent radiotherapy (median 36 Gy (range 21-54 Gy)) with lower median dose delivered with whole ventricle irradiation (12/18patients) than craniospinal irradiation (5/18patients). Sixteen patients received chemotherapy preceding radiotherapy. All patients are alive at median 7.25 years from primary treatment completion (range 2.03-13.1 years). Relapse occurred in three patients (16.67%) following treatment response, all of whom achieved remission following high-dose chemotherapy with stem-cell support and craniospinal radiotherapy. Post-treatment functional outcomes were similarly excellent. PD-L1 expression was low (1-49% cells) or negative in 87% of tumours tested but results were confounded by specimen quality and availability. Reduced-dose radiotherapy with chemotherapy does not compromise outcome and is standard of care at this institution. Immunotherapy is unlikely to become standard treatment in the near future.

Quality improvement in paediatric radiation oncology through peer review.

INTRODUCTION: Around 300 children in Australia and New Zealand (ANZ) undergo a course of radiation treatment (RT) each year. A fortnightly videoconference for radiation oncologists managing children started in 2013. We conducted an audit of the videoconference to assess its influence on the care of children who receive RT in ANZ. METHODS: De-identified data from minutes (August 2013-December 2019) were analysed retrospectively using three categories: meeting participation, case presentations and management decisions. RESULTS: There were 119 meetings and 334 children discussed over the six-year audit period with regular attendance from four of 11 centres treating children in ANZ. Most cases (80%) were discussed prior to RT. A change in the overall management plan was recommended for around one in eight patients (35/334, 13%). RT plan reviews were performed in 79 cases (23%). Adjustments were made to the target volume contours or treatment plan in 8% (6/79). CONCLUSION: Increasing the frequency of the meeting to weekly and compliant with the RANZCR Peer Review Audit Tool has the capacity to review all paediatric RT patients in ANZ prior to RT and initiate changes for as many as one in eight children treated by RT each year. The meeting should be considered a core component necessary to maintain expertise in paediatric RT in all centres providing RT for children in ANZ while also acting as a proton referral panel as more children are referred abroad for proton therapy before the Australian Bragg Centre for Proton Therapy opens in Adelaide in 2024.

Investigating the use of image thresholding in brachytherapy catheter reconstruction.

This study evaluated the accuracy of image thresholding in the reconstruction of catheters in brachytherapy treatment planning systems. Six test cases including four planar catheter configurations, an interstitial prostate and an intracavitary treatment plan were made use of in this study. The four planar CT scanned catheter arrangements included; catheters placed approximately 1, 0.5 cm apart, catheters closely arranged in a plan (<0.5 cm apart) and a loop arrangement. The intracavitary plan consisted of catheters arranged inside a mould configuration. All reconstruction methods were based on tracking wire markers placed inside the plastic catheters. Each of these catheter arrangements was reconstructed using an existing window adjustment technique (manual reconstruction) in the treatment planning system followed by a CT-based automated thresholding technique available in the same planning system. A corresponding reconstructed catheter was created using a segmented catheter structure using image thresholding from another planning system within the same department. Co-ordinates from all the reconstructed catheters were compared against each other to assess the geometric shift between manual and threshold based reconstruction on each transaxial image using in-house software and the maximum variations were recorded for assessment. It was observed in general that automated thresholding technique could assist in catheter reconstruction for catheters which are greater than 0.5 cm apart. The segmented thresholding method reported smaller variations when compared to the manual reconstruction using window adjustment technique. Automated reconstruction saves time in the brachytherapy planning, however it was noted that it is not feasible for closely spaced catheters. Segmented catheter reconstruction although time consuming, did provide a better alternative in most cases.

Comparison of CT-based volumetric dosimetry with traditional prescription points in the treatment of cervical cancer with PDR brachytherapy.

INTRODUCTION: The traditional use of two-dimensional geometric prescription points in intracavitary brachytherapy planning for locally advanced cervical cancer is increasingly being replaced by three-dimensional (3D) planning. This study aimed to directly compare the two planning methods to validate that CT planning provides superior dosimetry for both tumour and organs at risk (OARs) in our department. METHODS: The CT planning data of 10 patients with locally advanced cervical cancer was audited. For each CT dataset, two new brachytherapy plans were created, comparing the dosimetry of conventional American Brachytherapy Society points and 3D-optimised volumes created for the high-risk clinical target volume (HR CTV) and OARs. Total biologically equivalent doses for these structures were calculated using the modified EQD2 formula and comparative dose-volume histogram (DVH) analysis performed. RESULTS: DVH analysis revealed that for the 3D-optimised plans, the prescription aim of D90 ≥ 100% was achieved for the HR CTV in all 10 patients. However, when prescribing to point A, only 50% of the plans achieved the minimum required dose to the HR CTV. Rectal and bladder dose constraints were met for all 3D-optimised plans but exceeded in two and one of the conventional plans, respectively. CONCLUSIONS: This study confirms that the regionally relevant practice of CT-based 3D-optimised planning results in improved tumour dose coverage compared with traditional points-based planning methods and also improves dose to the rectum and bladder.

A unique approach to high-dose-rate vaginal mold brachytherapy of gynecologic malignancies.

PURPOSE: Patients with cervical and vaginal cancer sometimes have a less straightforward approach for choice of brachytherapy treatment owing to the tumor's location and clinical presentation. The staff at Royal Brisbane & Women's Hospital in Queensland, Australia, is trying to solve this problem by the use of an old technique in a new approach called vaginal molds. With a patient-specific vaginal mold, the appearance of the applicator and the dose distribution can be customized to provide an optimal treatment for each patient. METHODS AND MATERIALS: The technique used at the Royal Brisbane & Women's Hospital uses a flexible two-part putty, moulded to the shape of the vagina, in which standard catheters (flexible implant tubes) are incorporated, in a pattern designed to permit a dose distribution more conformal to the target volume. RESULTS: The presented technique is efficient and improves the accuracy of a homogeneous target cover and sparing of organs at risk for vaginal mold brachytherapy treatments at our institution. CONCLUSION: This technique offers a customizable option when traditional cylindrical- or dome-type applicators cannot be used, or provide inadequate dose coverage. Molds to match the patient anatomy can be created quickly, while allowing flexibility in positioning of catheters to achieve the desired dose distribution.

Natural oil-based emulsion containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer: a phase 3, double-blind, randomized, controlled trial.

PURPOSE: To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation-induced skin reactions. METHODS AND MATERIALS: A total of 174 patients were randomized and participated in the study. Patients received either cream 1 (the natural oil-based emulsion containing allantoin) or cream 2 (aqueous cream). Skin toxicity, pain, itching, and skin-related quality of life scores were collected for up to 4 weeks after radiation treatment. RESULTS: Patients who received cream 1 had a significantly lower average level of Common Terminology Criteria for Adverse Events at week 3 (P<.05) but had statistically higher average levels of skin toxicity at weeks 7, 8, and 9 (all P<.001). Similar results were observed when skin toxicity was analyzed by grades. With regards to pain, patients in the cream 2 group had a significantly higher average level of worst pain (P<.05) and itching (P=.046) compared with the cream 1 group at week 3; however, these differences were not observed at other weeks. In addition, there was a strong trend for cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison with cream 1 (P=.056). Overall, more participants in the cream 1 group were required to use another topical treatment at weeks 8 (P=.049) and 9 (P=.01). CONCLUSION: The natural oil-based emulsion containing allantoin seems to have similar effects for managing skin toxicity compared with aqueous cream up to week 5; however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching, and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream seems to be a more preferred option.

A double-blind randomised controlled trial of a natural oil-based emulsion (Moogoo Udder Cream®) containing allantoin versus aqueous cream for managing radiation-induced skin reactions in patients with cancer.

BACKGROUND: Radiation-induced skin reaction (RISR) is one of the most common and distressing side effects of radiotherapy in patients with cancer. It is featured with swelling, redness, itching, pain, breaks in skin, discomfort, and a burning sensation. There is a lack of convincing evidence supporting any single practice in the prevention or management of RISR. METHODS/DESIGNS: This double-blinded randomised controlled trial aims to investigate the effects of a natural oil-based emulsion containing allantoin (as known as Moogoo Udder Cream®) versus aqueous cream in reducing RISR, improving pain, itching and quality of life in this patient group. One group will receive Moogoo Udder Cream®. Another group will receive aqueous cream. Outcome measures will be collected using patient self-administered questionnaire, interviewer administered questionnaire and clinician assessment at commencement of radiotherapy, weekly during radiotherapy, and four weeks after the completion of radiotherapy. DISCUSSION: Despite advances of radiologic advances and supportive care, RISR are still not well managed. There is a lack of efficacious interventions in managing RISR. While anecdotal evidence suggests that Moogoo Udder Cream® may be effective in managing RISR, research is needed to substantiate this claim. This paper presents the design of a double blind randomised controlled trial that will evaluate the effects of Moogoo Udder Cream® versus aqueous cream for managing in RISR in patients with cancer. TRIAL REGISTRATION: ACTRN 12612000568819.

Tubular breast carcinoma: an argument against treatment de-escalation.

PURPOSE: To evaluate the role of adjuvant radiotherapy in management of patients with tubular carcinoma of the breast. METHODS: One hundred seventy-eight patients treated for tubular carcinoma were identified from the Queensland Radium Institute database. A retrospective review of medical records identified 115 patients meeting eligibility criteria: breast-conserving surgery for a histological diagnosis of tubular carcinoma, minimum follow up of 12 months and adequate medical records. RESULTS: Median follow up was 64 months. There were no significant differences between patient characteristics treated with and without radiotherapy. Median age at diagnosis was 54 (36-78) years. Ninety-five percent tumours were T1 and four patients had positive axillary lymph nodes. Of 94 patients treated with adjuvant radiotherapy, one developed local relapse. Five of 21 patients who did not have adjuvant radiotherapy failed locally. Five-year relapse-free survival with and without radiotherapy was 100 and 89%, respectively (hazard ratio for radiotherapy: 0.06; 95% confidence interval 0.01-0.32, P = 0.001). CONCLUSION: Radiotherapy has a significant impact on relapse-free survival in patients treated with breast-conserving surgery for tubular carcinoma.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma.

OBJECTIVE: Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. METHODS: This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m(2)) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. RESULTS: Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1-3 disease (44.8%) recurred (average follow-up 28.1 months, range 8-60 months). CONCLUSION: This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

Dosimetric effect of external beam planning preceding combined high-dose-rate brachytherapy of the prostate.

PURPOSE: The sequencing of external beam radiotherapy (EBRT) and a high-dose-rate brachytherapy (HDRB) boost is often interchangeable in clinical practice. When given before EBRT, HDRB could induce volume alterations in the prostate, which may have significant implications for EBRT dosimetry. We aimed to assess the influence of HDRB on prostate volume and, hence, prostate dosing via subsequent EBRT. METHODS AND MATERIALS: Fifteen men had both pre- and post-HDRB CT performed followed by EBRT. After deidentification, the clinical target volume (CTV) was defined on each CT by a single-blinded observer. Volumes were compared for the pre- and post-HDRB scans in each patient. Radiotherapy planning was performed using the prebrachytherapy volumes aiming for the planning target volume (PTV) to be covered by 43.7Gy. After soft-tissue coregistration, this plan was also applied to the postbrachytherapy volumes. RESULTS: Median volume increase was 35.4% for the CTV after HDRB. No patient experienced a decrease in CTV volume (range, 0-79% volume increase; p-value<0.001). Median volume increase was 26.1% for the PTVs, with no volume decrease observed (range, 8-56%; p<0.001). PTV proportion achieving dose target (V43.7Gy) decreased by median of 7% (range, 0-21.5%; p=0.004). The minimum dose to the PTV (D(100)%) decreased by a median of 6Gy (range, 0.5-16Gy; p<0.001). CONCLUSIONS: Insertion of HDRB catheters exerts substantial acute volumetric distortion on the prostate. EBRT planning performed on the basis of pre-HDRB imaging only inherently risks underdosing tumor. Planning adjustments based on repeat CT, or dedicated post-HDBT planning, is warranted for men managed with HDRB before EBRT.

A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET.

We undertook this study to estimate the event-free survival (EFS) of patients with newly diagnosed supratentorial primitive neuroectodermal tumor (SPNET) treated with risk-adapted craniospinal irradiation (CSI) with additional radiation to the primary tumor site and subsequent high-dose chemotherapy supported by stem cell rescue. Between 1996 and 2003, 16 patients with SPNET were enrolled. High-risk (HR) disease was differentiated from average-risk (AR) disease by the presence of residual tumor (M(0) and tumor size > 1.5 cm(2)) or disseminated disease in the neuraxis (M(1)-M(3)). Patients received risk-adapted CSI: those with AR disease received 23.4 Gy; those with HR disease, 36-39.6 Gy. The tumor bed received a total of 55.8 Gy. Subsequently, all patients received four cycles of high-dose cyclophosphamide, cisplatin, and vincristine with stem cell support. The median age at diagnosis was 7.9 years; eight patients were female. Seven patients had pineal PNET. Twelve patients are alive at a median follow-up of 5.4 years. The 5-year EFS and overall survival (OS) estimates for all patients were 68% +/- 14% and 73% +/- 13%. The 5-year EFS and OS estimates were 75% +/- 17% and 88% +/- 13%, respectively, for the eight patients with AR disease and 60% +/- 19% and 58% +/- 19%, respectively, for the eight with HR disease. No deaths were due to toxicity. High-dose cyclophosphamide-based chemotherapy with stem cell support after risk-adapted CSI results in excellent EFS estimates for patients with newly diagnosed AR SPNET. Further, this chemotherapy allows for a reduction in the dose of CSI used to treat AR SPNET without compromising EFS.

Disease-free survival after vaginal vault brachytherapy versus observation for patients with node-negative intermediate-risk endometrial adenocarcinoma.

PURPOSE: To compare the disease-free survival (DFS) of patients with surgical stage 1, intermediate-risk endometrial adenocarcinoma (EAC) treated with primary surgery with or without adjuvant vaginal vault brachytherapy (VVBT). PATIENTS AND METHODS: A retrospective chart review identified 575 patients with stage 1B, 1C or 2A endometrial cancer who had surgery between 1990 and 2004. All patients were surgically staged and 259 patients received postoperative VVBT. The date and site of first recurrence were considered the primary statistical endpoints and were analysed by univariate and multivariate Cox models. Subgroups of patients stratified by substage and grade were created and Log-rank tests using vaginal recurrence as the endpoint were calculated within these groups. RESULTS: After a mean follow-up period of 72 months (95%-confidence interval (CI): 68 to 75 months) a total of 43 (7.5%) patients developed recurrence. Multivariate analysis demonstrated that increasing patient's age at diagnosis and stage 1C or 2A disease were independent risk factors for recurrence whereas the grade of differentiation and the type of treatment (surgery alone vs. surgery followed by postoperative VVBT) were not associated with a change in DFS. Analysis within the subgroups stratified by substage and grade did not even reveal a trend towards improved local control with VVBT. CONCLUSION: Postoperative VVBT was not associated with a measurable reduction in the risk of recurrence in surgical stage 1, intermediate-risk endometrial cancer.