Impact of immobilisation and image guidance protocol on planning target volume margins for supine craniospinal irradiation

Background: The setup errors during supine-CSI (sCSI) using single or dual immobilisation (SM, DM) subsets from two institutions were reviewed to determine if DM consistently decreased the required planning target volumes (PTV) margins and to identify the optimal image guidance environments. Materials and methods: Ours and a sister institutional cohort, each with a subset of SM or DM sCSI and daily 3-dimensional online image verification sets, were reviewed for the cranial and spinal regions translational shifts. Using descriptive statistics, scatter plots and independent sample Mann-Whitney test we compared shifts in each direction for two subsets in each cohort deriving PTV margins (Van Herk: VH, Strooms: St recipes) for the cranial and spinal regions. Three image guidance (IG) protocols were simulated for two regions on the combined cohort with SM and DM subsets to identify the most optimal option with the smallest PTV margin. The IG protocols: 3F, 5F and 5FB where the systematic error correction was done using the average error from the first three, five and in the cranium alone (applied to both the cranium and spine, otherwise) for the first five set-ups, respectively. Results: 6968 image sets for 179 patients showed DM could consistently reduce the PTV margin (VH/St) for the cranium from 6/5 to 4/3.5 (31.8/30.8%) and 6/4 to 4/3.5 mm (30.5/16.8%) for primary and validation cohort, respectively. Similarly, for the spine it was 10/8.5 to 6/5.5 (38.6/38.4%) and 9/7.7 to 7/6 (21.6/21.4%), respectively. The “5F-IG” resulted in the smallest margins for both the cranial (3 mm) and spinal region (5 mm) for DM with estimated 95% CTV coverage probability. Conclusion: DM with 5F-IG would significantly reduce the required PTV margins for sCSI

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively (P < .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy. (C) 2017 by American Society of Clinical Oncolog

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180). Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a broad spectrum of histologies and sites, including midline locations, which are not often routinely biopsied in clinical practice. Patients with BRAF V600E PLGG exhibited poor outcomes after chemotherapy and radiation therapies that resulted in a 10-year progression-free survival of 27% (95% CI, 12.1% to 41.9%) and 60.2% (95% CI, 53.3% to 67.1%) for BRAF V600E and wild-type PLGG, respectively ( P \u3c .001). Additional multivariable clinical and molecular stratification revealed that the extent of resection and CDKN2A deletion contributed independently to poor outcome in BRAF V600E PLGG. A similar independent role for CDKN2A and resection on outcome were observed in the independent cohort. Quantitative imaging analysis revealed progressive disease and a lack of response to conventional chemotherapy in most patients with BRAF V600E PLGG. Conclusion BRAF V600E PLGG constitutes a distinct entity with poor prognosis when treated with current adjuvant therapy

Molecular insights turning game for management of ependymoma: A review of literature

Molecular biology of ependymoma is being extensively studied in recent years, providing insights into newer therapeutic strategies. The different anatomic subgroups of ependymoma, namely supratentorial, posterior fossa (PF), and spinal, pose entirely different clinical behavior and prognosis. Recently, nine molecular subgroups of ependymoma have been identified, one of which has been incorporated into the WHO classification. Further understanding of the molecular biology of ependymoma is vital to expand its clinical utility. Here, we performed a review of the literature on the molecular biology of ependymoma. Therapeutic avenues include: (1) targeted agents against – (a) chromothripsis-induced nuclear factor-kappa beta signaling, (b) gene silencing by DNA methylation, (c) increased telomerase activity, and (d) microRNA and (2) de-escalating treatment in good prognostic subgroup such as PFB. The prognostic value of different chromosomal gain or loss is being better understood and may serve as prognostic signatures in future. Faster adoption of molecular classification into clinical practice requires simpler identification techniques using immunohistochemical surrogates for molecular subgroups, for example, cell adhesion molecule L1 for v-rel reticuloendotheliosis viral oncogene homolog A (RELA) fusion, laminin subunit alpha 2, tenascin-C, and neural epidermal growth factor-like 2 for PFA and PFB. Identification of poor prognostic markers such as RELA fusion and PFA has necessitated future research impetus to be directed to find more efficacious treatment approach in these groups

Electron beam radiotherapy for the management of recurrent extensive ocular surface squamous neoplasia with orbital extension

Recurrent extensive ocular surface squamous neoplasia (OSSN) with orbital invasion can be successfully managed with external radiotherapy using electrons resulting in eye and vision salvage. We report a case of right eye recurrent OSSN in an immunocompetent adult Indian male, with extensive orbital involvement. The patient had two previous surgical excisions with recurrent disease. At this stage, conventionally exenteration is considered the treatment modality. However, he was treated with 5040 cGy radiotherapy (15eV electrons) resulting in complete disease regression. At the end of 3 years follow-up, the patient was disease free, maintained a vision of 20/25, with mild dry eye, well-managed with topical lubricants. Extensive OSSN with orbital invasion does not always need exenteration. External beam electron radiotherapy provides a noninvasive cure with organ and vision salvage and should be considered in extensive OSSN not amenable to simple excision biopsies. Long-term studies to evaluate the effect of radiation on such eyes are suggested

Helical tomotherapy-based hypofractionated radiotherapy for prostate cancer: A report on the procedure, dosimetry and preliminary clinical outcome

Context: Hypofractionated intensity-modulated radiotherapy (IMRT) under image guidance using helical tomotherapy for prostate cancer improves therapeutic ratio. Aims: To report on clinical and dosimetric experience using hypofractionated helical tomotherapy for prostate cancer. Settings and Design: Prospective consecutive case series as feasibility study approved by Institutional Review Board (IRB) (2007-11). Materials and Methods: The staging work-up, risk stratification, simulation, contouring, planning, online matching and treatment delivery methodology are described in detail. The doses to (prostate and nodal) PTV and organs at risk (bladder, rectum, bowel and femoral heads) are described. The audit of online matching was used to determine set-up errors, PTV margins and resultant translational vector. We also report the outcomes in terms of biochemical relapse-free survival and acute toxicity. Results: Fifty-three consecutive patients were included. The baseline PSA was 23 ng/ml (1.60-100.37). The prostate BED3 ranged from 110-129 Gy (α/β for prostate 1.5-3 Gy) and nodal 72-87.68 Gy. The required PTV margin by van Hark′s formula for lateral, longitudinal and vertical axes were 11.30, 9.95 and 13.49 mm, respectively with resultant vectors 3-15 mm. There was 7% to 8% chance of missing part of CTV in absence of image guidance. There was only one patient requiring premature conclusion at 45 Gy due grade 3 genitourinary toxicity. At median follow-up of 23 months, biochemical relapse-free survival rate is 95.2%. Conclusions: Hypofractionated IMRT under image guidance using helical tomotherapy for prostate cancer is feasible with acceptable acute toxicity and may be advantageous in high throughput centers

Adopting Health Economic Research in Radiation Oncology: A Perspective From Low- or Middle-Income Countries

Establishing a new radiation therapy (RT) setup is resource-intensive as it involves substantial capital costs and the recruitment of a skilled workforce. It is essential to incorporate health economic analysis that estimates recurring and nonrecurring expenses on the basis of the national and local needs, infrastructure, and future projections. RT costing exercises can be especially relevant for low- or middle-income countries (LMICs) with more than 70% of the global cancer burden, with access to < 20% of the available resources. This review article summarizes the scope of RT costing exercises in LMICs, the hurdles in conducting them, and possible ways to circumvent them. The purpose of performing costing studies in RT lies in their utility to improve the efficiency of the investment while at the same time helping to address the issues of uniformity and equitable distribution of resources. This will help assess the net benefit from RT in terms of utility and outcome-linked parameters like Quality-Adjusted Life Years. There are numerous barriers to conducting economic evaluations in LMICs, including the lack of national costing values for equipment, data on manpower salary, cost for public and private setups, and indirect costs. The situation is further complicated because of the nonuniform pay structure, lack of an organizational framework, robust real-world data on outcomes, and nonavailability of country-specific reference utility values. Collaborative national efforts are required to collect all elements required to perform health technology assessments. Information from the national and hospital databases can be made available in the public domain to ease access and broader adoption of health economic end points in routine care. Although resource-intensive at the onset, costing studies and health economic assessments are essential for improving the coverage and quality of RT in LMICs