Intellectual changes after radiation for children with brain tumors: which brain structures are most important?

BACKGROUND: The objective of this study was to evaluate the contribution of radiation dose to different intracranial structures on changes in intellectual function for children with brain tumors. METHODS: We evaluated children with brain tumors treated in 2005-2017 who had longitudinal neuropsychological assessments and available photon dosimetric data (if radiation therapy [RT] given). Full Scale Intelligence Quotient (FSIQ) and index scores were evaluated (perceptual reasoning index [PRI], processing speed index [PSI], verbal comprehension index [VCI], and working memory index [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at RT and dose to different brain regions as fixed effects and patient-specific random intercepts. P-values (P*) were adjusted for multiple comparisons. RESULTS: Sixty-nine patients were included, 56 of whom received RT. Median neuropsychological follow-up was 3.2 years. Right temporal lobe mean dose was strongly associated with decline in FSIQ (P* = 0.005); with each gray increase in mean dose, there was a decrease of 0.052 FSIQ points per year. Dose to 50% (D50) of the supratentorial brain was associated with decline in PSI (P* = 0.006) and WMI (P* = 0.001). Right and left hippocampus D50 were individually strongly associated with declines in VCI (P* = 0.009 for each). Presence of a ventriculoperitoneal shunt decreased FSIQ by 10 points. CONCLUSIONS: We reported associations between dosimetry to specific brain regions and intellectual outcomes, with suggested avoidance structures during RT planning. These models can help clinicians anticipate changes in neurocognition post-RT and guide selection of an optimal RT plan.

Application of stereotactic body radiotherapy in advanced pancreatic cancers in Australia.

INTRODUCTION: The majority of pancreatic cancers present locally advanced and carry a high mortality rate. Treatment is challenging, with mixed data suggesting use of chemotherapy alone or in combination with radiotherapy. The use of radiotherapy has previously been limited due to lack of ability to deliver radiation to the tumour mass without causing significant toxicity to surrounding organs. Stereotactic body radiotherapy (SBRT) allows delivery of higher biologically equivalent dose in a shorter treatment duration. We sought to investigate the safety and application of this technique in our centre. METHOD: We enrolled 27 patients from 2015, identified as locally advanced unresectable with histologically confirmed, non-metastatic, pancreatic adenocarcinoma. All patients had endoscopically inserted fiducial markers and where possible concurrent chemotherapy was administered. Dose schedules ranged from 25 to 42 Gy in 5 or 3 fractions. RESULTS: With an overall median follow up of 9 months (range, 3-32.7), the median survival was 11.6 months. Of those alive at 1 year, the local control rate was 67%. Six patients had Grade 3 toxicity, and other six had Grade 2 toxicity. None had Grade 4 or above toxicity. The most common symptom recorded was fatigue. CONCLUSION: SBRT for locally advanced pancreatic cancer is technically complex but feasible in a high volume centre. SBRT is unique, allowing safe delivery of high radiation dose resulting in good local control and decreases treatment time making it an attractive option for patients with unresectable pancreatic cancer.

Phase II study of celecoxib with docetaxel chemoradiotherapy followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer.

TITLE: Phase II study of celecoxib with docetaxel chemoradiotherapy (CRT) followed by consolidation chemotherapy docetaxel plus cisplatin with maintenance celecoxib in inoperable stage III nonsmall cell lung cancer. INTRODUCTION: Concurrent CRT has been associated with improvement in absolute 5-year survival by 10% and is the standard of care for inoperable stage III nonsmall cell lung cancer. Preclinical evidence suggests that cyclooxygenase-2 inhibition may increase the efficacy of CRT. METHODS: Patients were treated with CRT (weekly docetaxel at 30 mg/m2 over 6 weeks with concurrent external beam radiotherapy with 60 Gy in 30 fractions) followed by consolidation chemotherapy with docetaxel and cisplatin, each at 75 mg/m2 given 3 weekly for four cycles. Patients were to receive celecoxib 400 mg twice daily during treatment. Prophylactic cranial irradiation (30 Gy in 15 fractions) was offered if there was disease response. RESULTS: Twenty-four patients commenced CRT. Nineteen patients commenced consolidation therapy with 14 patients completing treatment. Twelve patients had treatment with celecoxib. In the total cohort, the median overall survival (mOS) was 21 months and progression-free survival (PFS) was 16 months. Overall response rate was 59% and disease control rate was 82%. Three patient deaths occurred. Significant grade 3/4 toxicity included radiation pneumonitis (17%), febrile neutropenia (17%), infection/sepsis with or with neutropenia (25%) and esophagitis (12.5%). Retrospective analysis of celecoxib versus no celecoxib treatment showed favorable mOS 26.5 versus 17.5 months and PFS 22 versus 16 months, but this did not reach statistical significance. CONCLUSIONS: The activity of this regimen has been demonstrated. Treatment-related toxicity was substantial. The role of celecoxib in addition to CRT could not be demonstrated in this study because of the small number of patients.

Are staging investigations being overused in patients with low and intermediate risk prostate cancer?

INTRODUCTION: According to international best practice guidelines, staging abdominal and pelvic computed tomography (CTAP) and whole body bone scan (WBBS) are not recommended for asymptomatic low and intermediate-risk prostate cancer. Despite this, many patients undergo these investigations. Our aim was to determine the rate and cost of scans being performed for this group of patients. METHOD: We utilised a database of prostate cancer patients treated by a radiation oncologist specialising in prostate cancer at the Royal Adelaide Hospital between January 2008 and December 2012. Risk criteria were defined according to the D'Amico system. We identified the staging investigations ordered. RESULTS: Of 236 consecutive eligible patients, 69 (70%) and 85 (86%) of 99 low risk, and 112 (82%) and 126 (92%) of 137 intermediate-risk patients, were found to have had staging CTAP and WBBS, respectively. In fact, only 9.7% of the patients followed the international best practice guidelines and had no staging investigations. None of these scans showed evidence of metastatic disease. The total costs of these investigations for the low and intermediate-risk groups were approximately AUD 75 000 and AUD 116 000, respectively. CONCLUSION: We found that there is clearly a significant overuse of staging investigations for both these groups while the incidence of metastases identified was very low. This is likely to have a significant impact on the waiting time for scans and lead to substantial waste of resources. It places unnecessary financial burden on the patients and the healthcare system. There are also issues of increased radiation and contrast exposure, and potentially unnecessary further investigations.

Quality indicators for prostate radiotherapy: are patients disadvantaged by receiving treatment in a 'generalist' centre?

INTRODUCTION: The purpose of this retrospective review was to evaluate concordance with evidence-based quality indicator guidelines for prostate cancer patients treated radically in a 'generalist' (as distinct from 'sub-specialist') centre. We were concerned that the quality of treatment may be lower in a generalist centre. If so, the findings could have relevance for many radiotherapy departments that treat prostate cancer. METHODS: Two hundred fifteen consecutive patients received external beam radiotherapy (EBRT) and/or brachytherapy between 1.10.11 and 30.9.12. Treatment was deemed to be in line with evidence-based guidelines if the dose was: (i) 73.8-81 Gy at 1.8-2.0 Gy/fraction for EBRT alone (eviQ guidelines); (ii) 40-50 Gy (EBRT) for EBRT plus high-dose rate (HDR) brachytherapy boost (National Comprehensive Cancer Network (NCCN) guidelines); and (iii) 145 Gy for low dose rate (LDR) I-125 monotherapy (NCCN). Additionally, EBRT beam energy should be ≥6 MV using three-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT), and high-risk patients should receive neo-adjuvant androgen-deprivation therapy (ADT) (eviQ/NCCN). Treatment of pelvic nodes was also assessed. RESULTS: One hundred four high-risk, 84 intermediate-risk and 27 low-risk patients (NCCN criteria) were managed by eight of nine radiation oncologists. Concordance with guideline doses was confirmed in: (i) 125 of 136 patients (92%) treated with EBRT alone; (ii) 32 of 34 patients (94%) treated with EBRT + HDR BRT boost; and (iii) 45 of 45 patients (100%) treated with LDR BRT alone. All EBRT patients were treated with ≥6 MV beams using 3D-CRT (78%) or IMRT (22%). 84%, 21% and 0% of high-risk, intermediate-risk and low-risk patients received ADT, respectively. Overall treatment modality choice (including ADT use and duration where assessable) was concordant with guidelines for 176/207 (85%) of patients. CONCLUSION: The vast majority of patients were treated concordant with evidence-based guidelines suggesting that, within the limits of the selected criteria, prostate cancer patients are unlikely to be disadvantaged by receiving radiotherapy in this 'generalist' centre.