Long-term outcomes of symptomatic optic pathway glioma: 32-year experience at a single Western Australian tertiary pediatric oncology center.

Introduction: Optic pathway gliomas (OPGs) are associated with significant risk of visual and endocrine morbidity, but data on long-term outcomes in symptomatic patients is sparse. This study reviews the clinical course, disease progression, survival outcomes and long-term sequelae in pediatric patients with symptomatic OPGs in our institution over three decades. Methods: Retrospective review of patients with symptomatic OPG treated in a single tertiary pediatric oncology center from 1984 to 2016. Results: A total of 37 patients were diagnosed with symptomatic OPG. Decreased visual acuity was the commonest presenting symptom (75.7%). Surgical intervention was performed in 62.2%; 56.5% underwent biopsy, 26.1% surgical debulking and 17.4% had orbital decompression with cystic fenestration and cosmetic optic nerve excision at different treatment intervals. CSF diversion was performed in 47.8% patients. Histopathologic examination confirmed 86% to be pilocytic astrocytoma and 1 ganglioglioma. 46% received chemotherapy and 48% had radiotherapy, at different intervals. Median follow-up was 13.74 years. In NF1 patients, overall survival (OS) was 100% at 5 years and 55.6 ± 24.8% at 25 years while progression-free-survival (PFS) was 50 ± 15.8% at 5 and 20 years. In non-NF1 patients, OS was 96.2 ± 3.8% at 5 years and 87.4 ± 9% at 25-years. 5-year PFS was 53.8 ± 9.8% and 25-year PFS was 49.0 ± 10%. Cumulative PFS was 53 ± 8.3% at 5 years and 49.7 ± 8.4% at 20 years while cumulative OS was 97.2 ± 2.7% at 5 years and 77.5 ± 10.8% at 25 years. 59.5% patients developed post-operative endocrinopathy. Long-term vision was normal in 8.1%, improved in 13.5%, stabilized in 40.5% but worsened in 37.8% patients. Three patients treated with radiotherapy developed second brain tumors. Conclusion: 25-year OS in this cohort was 77.5% but survivorship carried significant long-term morbidities including radiation-induced second malignant brain tumors.

Treatment and outcomes for synovial sarcoma patients in Western Australia: the role of neoadjuvant chemoradiotherapy.

BACKGROUND: This is a retrospective review of synovial sarcoma (SS) patients treated over the last 12 years in Western Australia (WA). SS is both chemo and radiotherapy sensitive. Results of trials in adjuvant chemotherapy are conflicting and there is limited support for neoadjuvant chemotherapy. The use of combined chemoradiotherapy is based on institutional preferences. AIM: We reviewed the outcomes for SS patients treated in WA over a 12 year period focusing on patients who received neoadjuvant chemoradiotherapy (NACRT). METHODS: Patient details including demographics, histopathology, treatment details, were obtained from the WA sarcoma database (2006-2018). Progression free survival (PFS) and overall survival (OS) were derived for whole cohort. RESULTS: Twenty seven patients were identified with SS with equal gender incidence. Median age of the cohort was 36 (14-76) years. The most common primary site of disease was extremity (81.5%). 22/27 patients presented with only localized disease and 59.2% of these received neo-adjuvant treatment. Of those who received neoadjuvant treatment, 56.2% had NACRT, while 25.0% and 18.7% of patients had chemotherapy and radiotherapy respectively. Mesna, doxorubicin, ifosfamide, dacarbazine (MAID) was the most commonly used chemotherapy regimen as neoadjuvant or adjuvant treatment while ifosfamide (93.7%) was the most commonly used chemotherapy drug in any setting. There was no reported case of disease progression in group of patients who received NACRT apart from one patient who had oligometastatic disease at diagnosis. Median OS of the whole cohort was 38 months while median PFS was 24 months. Bone marrow toxicity was the most commonly reported high grade toxicity in NACRT group (55.5%) but there were no treatment related deaths. CONCLUSION: NACRT is not widely adopted and treatment is based on institutional preferences, however our data shows that NACRT is a feasible therapy option. NACRT should be evaluated prospectively in a randomized trial.

Compliance with multidisciplinary team meeting management recommendations.

OBJECTIVES: The objective of this study was to evaluate patient compliance with management recommendations given by a breast cancer multidisciplinary team (MDT), assess for reasons for noncompliance, and perform an exploratory assessment on breast cancer outcomes in noncompliant patients. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data was undertaken for patients selected by their primary clinician to be discussed at the MDT of Breast Cancer Research Centre-WA in Perth between 1st March 2011 and the 28th February 2016. The primary objective was the rate of compliance with MDT management recommendations. Secondary objectives included factors associated with noncompliance, rate of clinical trial uptake, and impact of treatment noncompliance on breast cancer events in a subgroup of early breast cancer (EBC) patients. RESULTS AND CONCLUSION: A total of 2614 MDT management recommendations were made for 925 patients. Overall, 92% were compliant with all recommendations given. Clinical trial recruitment was successful in 84.1%. The reasons given for treatment noncompliance were fear of toxicity, choosing an alternative treatment, and treatment inconvenience. In a subset of 337 EBC patients, there was a significantly higher rate of contralateral breast cancer, distant recurrence, and breast cancer-specific death, P = .0016, in those who were noncompliant. Our study demonstrates a high rate of MDT treatment recommendation compliance and clinical trial recruitment. In a subgroup of EBC patients, noncompliance was associated with significantly worse outcomes. Attention to educating patients to minimize their fear of treatment toxicity and ensuring their understanding of evidence-based treatment may lead to lower rates of noncompliance.

Patient preferences for adjuvant radiotherapy in early breast cancer are strongly influenced by treatment received through random assignment.

OBJECTIVE: TARGIT-A randomised women with early breast cancer to receive external beam radiotherapy (EBRT) or intraoperative radiotherapy (TARGIT-IORT). This study aimed to identify what extra risk of recurrence patients would accept for perceived benefits and risks of different radiotherapy treatments. METHODS: Patient preferences were determined by self-rated trade-off questionnaires in two studies: Stage (1) 209 TARGIT-A participants (TARGIT-IORTn = 108, EBRTn = 101); Stage (2) 123 non-trial patients yet to receive radiotherapy (pre-treatment group), with 85 also surveyed post-radiotherapy. Patients traded-off risks of local recurrence in preference selection between TARGIT-IORT and EBRT. RESULTS: TARGIT-IORT patients were more accepting of IORT than EBRT patients with 60% accepting the highest increased risk presented (4%-6%) compared to 12% of EBRT patients, and 2% not accepting IORT at all compared to 43% of EBRT patients. Pre-treatment patients were more accepting of IORT than post-treatment patients with 23% accepting the highest increased risk presented compared to 15% of post-treatment patients, and 15% not accepting IORT at all compared to 41% of pre-treatment patients. CONCLUSIONS: Breast cancer patients yet to receive radiotherapy accept a higher recurrence risk than the actual risk found in TARGIT-A. Measured patient preferences are highly influenced by experience of treatment received. This finding challenges the validity of post-treatment preference studies.

Cosmetic outcome as rated by patients, doctors, nurses and BCCT.core software assessed over 5 years in a subset of patients in the TARGIT-A Trial.

BACKGROUND: The purpose of this research was to assess agreement between four rating systems of cosmetic outcome measured in a subset of patients with early breast cancer participating in the randomised TARGIT-A trial. TARGIT-A compared risk-adapted single-dose intra-operative radiotherapy (TARGIT-IORT) to whole breast external beam radiotherapy (EBRT). METHODS: Patients, their Radiation Oncologist and Research Nurse completed a subjective cosmetic assessment questionnaire before radiotherapy and annually thereafter for five years. Objective data previously calculated by the validated BCCT.core software which utilizes digital photographs to score symmetry, colour and scar was also used. Agreement was assessed by the Kappa statistic and longitudinal changes were assessed by generalized estimating equations. RESULTS: Overall, an Excellent-Good (EG) cosmetic result was scored more often than a Fair-Poor (FP) result for both treatment groups across all time points, with patients who received TARGIT-IORT scoring EG more often than those who received EBRT however this was statistically significant at Year 5 only. There was modest agreement between the four rating systems with the highest Kappa score being moderate agreement which was between nurse and doctor scores at Year 1 with Kappa = 0.46 (p < 0.001), 95% CI (0.24, 0.68). CONCLUSION: Despite similar overall findings between treatment groups and rating systems, the inter-rater agreement was only modest. This suggests that the four rating systems utilized may not necessarily be used interchangeably and it is arguable that for an outcome such as cosmetic appearance, the patient's point of view is the most important. TRIAL REGISTRATION: TARGIT-A ISRCTN34086741 , Registered 21 July 2004, retrospectively registered.

Cosmesis and Breast-Related Quality of Life Outcomes After Intraoperative Radiation Therapy for Early Breast Cancer: A Substudy of the TARGIT-A Trial.

PURPOSE: To report the first comprehensive investigation of patient-reported cosmesis and breast-related quality of life (QOL) outcomes comparing patients randomized to risk-adapted single-dose intraoperative radiation therapy (TARGIT-IORT) versus external beam radiation therapy (EBRT) on the TARGIT-A trial. METHODS AND MATERIALS: Longitudinal cosmesis and QOL data were collected from a subset of TARGIT-A participants who received TARGIT-IORT as a separate procedure (postpathology). Patients completed a cosmetic assessment before radiation therapy and annually thereafter for at least 5 years. Patients also completed the combined European Organization for Research and Treatment of Cancer (EORTC) core questionnaire and Breast-Specific Module in addition to the Body Image after Breast Cancer Questionnaire at baseline and annually thereafter. The combined EORTC questionnaires were also collected 3, 6, and 9 months after wide local excision. RESULTS: An Excellent-Good cosmetic result was scored more often than a Fair-Poor result for both treatment groups across all time points. The TARGIT-IORT patients reported better breast-related QOL than EBRT patients. Statistically and clinically significant differences were seen at month 6 and year 1, with EBRT patients having moderately worse breast symptoms (a statistically significant difference of more than 10 in a 100-point scale) than TARGIT-IORT patients at these time points. CONCLUSION: Patients treated with TARGIT-IORT on the TARGIT-A trial have similar self-reported cosmetic outcome but better breast-related QOL outcomes than patients treated with EBRT. This important evidence can facilitate the treatment decision-making process for patients who have early breast cancer suitable for breast-conserving surgery and inform their clinicians.

Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

Brief intervention: a promising framework for child and youth mental health?

There is a discrepancy between the demand for mental health treatment amongst children, young people and their carers, and the capacity of the current service system to provide evidence based interventions. Innovative models of care are required to redress this discrepancy. One such model is the single session model, which provides a single or small number of solution focused sessions targeting one or two identified problems. Single session interventions have been trialled across a range of presenting concerns including child and youth mental health services. This paper provides a rationale for offering a brief focused intervention as part of a broader Child and Youth Mental Health Service, and introduces a model of how brief intervention fits within a broader system of care.

Childhood craniopharyngioma: 20-year institutional experience in Western Australia.

AIM: A retrospective audit was undertaken to evaluate modes of presentation and treatment outcomes for craniopharyngioma in a single paediatric institution over a 20-year period. METHODS: A search of the neurosurgical and histopathological databases for patients under 21 years of age treated for craniopharyngioma between 1990 and 2010 was performed at our institution. The clinical records of eligible patients were reviewed and information regarding presentation, medical and surgical management and post-treatment outcome were extracted and collated. RESULTS: Of 10 evaluable patients, the commonest presenting symptoms were headache and visual impairment. Clinical and biochemical evaluation undertaken prior to surgery revealed visual dysfunction in 70% and pituitary deficit in 30%. Gross total resection was achieved in 40% but was curative in only 20%. The remaining 80% required further surgical and/or radiotherapeutic intervention. Seven patients had radiation therapy with stabilisation in 70%. Multiple pituitary hormone deficiency evolved in all patients over time, while visual impairment worsened in 30% post-operatively and improved in 20%. Obesity was present in 50% after a mean follow-up interval of 5.6 years and was apparent within 1 year of initial surgery in 30%. Although neurocognitive, psychological and behavioural problems were noted for some patients during medical review, only 20% of patients were formally assessed. CONCLUSIONS: Craniopharyngioma is associated with significant long-term morbidity. Attention to an integrated care pathway that includes standardised neurocognitive and psychological and behavioural assessment would facilitate early appropriate intervention and support leading to an improved quality of life for children with craniopharyngioma.

Development and pilot testing of a radiation therapist-led educational intervention for breast cancer patients prior to commencing radiotherapy.

AIM: To describe the development of the content and pilot testing of a radiation therapist-led educational intervention for breast cancer patients about to commence radiotherapy. Pilot testing consisted of testing the intervention for appropriateness, feasibility and acceptance. METHODS: A tailored intervention consisting of two face-to-face meetings with a radiation therapist (one before radiation planning, the other before treatment) was developed using Level I evidence for preparing patients for potentially threatening procedures. Training of intervention radiation therapists consisted of two communication skills workshops. Radiation therapists' consultations were tape-recorded and analyzed. The feasibility of the intervention was assessed by response rates and feedback from patients and radiation therapists. Patients completed surveys at baseline and following each intervention delivery. The main outcome measures were anxiety and depression, patient concerns and knowledge about radiotherapy. RESULTS: Response rates were considered acceptable. Twelve patients were enrolled and completed baseline measures. Nine patients completed follow-up measures following the second consultation. Preliminary results showed a trend for a decrease in anxiety and depression levels following the first consultation. There was also a decrease in concerns about radiotherapy and an increase in patients' knowledge. The instruments showed variability at baseline and discriminated between different responses over time. Radiation therapists adhered to providing the interventions. Interviews with radiation therapists and patients demonstrated that the intervention was feasible and acceptable. CONCLUSION: This pilot study demonstrated that this new intervention is both feasible and acceptable to radiation therapists and patients. The intervention is now being assessed using a randomized controlled trial.

Radiotherapy in the management of high-grade gliomas diagnosed in Western Australia: a patterns of care study.

PURPOSE: Radiotherapy (RT) plays an integral role in the management of high-grade glioma (HGG). However, there is little information on the patterns of care in unselected Australian patients with HGG. PATIENT AND METHODS: This prospective cohort study collected information on patients with a diagnosis of HGG managed in Western Australia over a 25-month period from 2006 to 2008. RT treatment and survival data were analysed. RESULTS: 86% of Western Australian patients with HGG were treated at the study site over this period. Of these, 80% were reviewed by a radiation oncologist with RT recommended in 88% of cases. One hundred eighty-seven patients proceeded to have RT, with most receiving 60 Gy in 30 fractions with limited field external beam radiotherapy (LFRT). Median survival from diagnosis was 13.6 months for all patients and 15.4 months for those planned for treatment with 60 Gy in 30 fractions. The median time from surgery to the start of RT was 41 days. Longer waiting times were not predictors of poor survival. Failure to receive all planned treatment (13% of patients) predicted for poor survival (hazard ratio 0.38). CONCLUSION: Dose and fractionation practices show concordance with published data and guidelines. Survival is also consistent with clinical trial data for patients planned for aggressive therapy. Nevertheless, a substantial number of patients are not suited to aggressive therapy or fail to complete planned therapy, and these patients have poor outcomes. Treatment delays did not affect survival outcomes but are confounded by earlier treatment of those unsuited to LFRT.

Information needs and preferences of women as they proceed through radiotherapy for breast cancer.

OBJECTIVE: While radiotherapy is commonly employed in the treatment of breast cancer, many women know little about treatment and experience treatment related anxiety. The aims of this study were to: Prioritise breast cancer patients' radiotherapy related information needs and concerns; determine unmet information needs; ascertain which information sources patients prefer to receive; and explore whether information provision reduces anxiety and depression. METHODS: A longitudinal survey was administered at four time points: after initial consultation with radiation oncologist, after the planning appointment, within first week of treatment and after treatment completion. Data was analysed using generalised estimating equations. RESULTS: 123 women participated. Women were most concerned about the impact treatment would have on their health in the future. Women identified high information needs prior to treatment planning and commencing treatment. Women's anxiety at baseline (mean=6.07, SD=3.89) did not significantly drop until after treatment commencement (mean=5.33, SD=4.15). CONCLUSION: This study demonstrates that women's information needs and anxiety levels are high until treatment commencement. PRACTICE IMPLICATIONS: In order to reduce patients' psychological distress, information needs and concerns we recommend that a greater focus is placed on providing information to patients prior to treatment planning and prior to treatment.

How to use a case manager--a partnership approach.

There is great scope for general practitioners and case managers to work together. An agreement regarding roles and responsibilities negotiated between GPs and service providers assists in the resource efficient provision of care and can result in positive outcomes for patients. This article describes how a GP can effectively use a case manager in a partnership approach.