We proposed that metabolic remodeling in the form of increased myocardial glucose analogue 2-[18F] fluoro-2deoxy-D-glucose (FDG) uptake precedes and triggers the onset of severe contractile dysfunction in pressure overload left ventricular hypertrophy (LVH) in vivo. To test this hypothesis we used a mouse model of transverse aortic constriction (TAC) together with Positron Emission Tomography (PET) and assessed serial changes in cardiac metabolism and function over 7 days. Methods PET scans of 16 C57BL/6 male mice were performed using a microPET scanner under sevofluorane anesthesia. A 10-minute transmission scan was followed by a 60-minute dynamic FDG-PET scan with cardiac and respiratory gating. Blood glucose levels were measured before and after the emission scan. Transverse aortic constriction (TAC) and sham surgeries were performed after baseline imaging. Osmotic mini-pumps containing either propranolol (5 mg/kg/day) or vehicle alone were implanted subcutaneously at the end of surgery. Subsequent scans were taken at days 1 and 7 after surgery. A compartment model, in which the blood input function with spill-over and partial volume corrections and the metabolic rate constants in a 3-compartment model are simultaneously estimated, was used to determine the net myocardial FDG influx constant, Ki. The rate of myocardial glucose use, rMGU, was also computed. Estimations of the ejection fractions (EF) were based on the high resolution gated PET images Results Mice undergoing TAC surgery exhibited an increase in the Ki (580%) and glucose usage the day after surgery indicating early adaptive response. On day 7 the EF had decreased by 24% indicating a maladaptive response. Average Ki increases were not linearly associated with increases in rMGU. Ki exceeded rMGU by 29% in the TAC mice. TAC Mice treated with propranolol attenuated rate of FDG uptake, diminished mismatch between Ki and rMGU (9%) and rescued cardiac function. Conclusions Metabolic maladaptation precedes the onset of severe contractile dysfunction. Both are prevented by treatment with propranolol. Early detection of metabolic remodeling may offer a metabolic target for modulation of hypertrophy.

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The QA tool assists users to detect potential delineation errors. QA tool integration into clinical procedures may reduce the frequency of inaccurate OAR delineation, and potentially improve safety and quality of radiation treatment planning.

Patients with intermediate to high risk disease (prostate specific antigen (PSA) ≥ 10, Gleason score ≥ 7, or clinical stage ≥ T2b) suffer from poorer long-term biochemical control (freedom from an increasing prostate specific antigen level) when treated with external beam radiation (EBRT) alone. In order to improve biochemical control while limiting long-term complications, brachytherapy has been incorporated into radiotherapy treatment, either alone or in combination with EBRT. Areas covered: Current literature regarding the use of high dose-rate (HDR) brachytherapy for localized prostate cancer, including as a boost and monotherapy. The efficacy and toxicities of various approaches are evaluated including comparisons to low dose-rate (LDR) brachytherapy. Expert commentary: Prostate HDR brachytherapy has higher conformality than EBRT, potentially improving the therapeutic ratio by allowing higher doses per fraction to tumor cells. The improved biochemical control shown in trials have resulted in EBRT plus brachytherapy to be included as a standard treatment option supported by the NCCN and ASCO guidance documents for intermediate to high risk prostate cancer.

Hemangiopericytomas are rare central nervous system (CNS) tumors. We sought to investigate existing clinical management strategies and overall survival (OS) among patients with hemangiopericytomas arising from the CNS. Materials/Methods: All patients diagnosed with CNS hemangiopericytoma from 2004-2014 in the National Cancer Database were included. Clinical and treatment-related characteristics were recorded and analyzed for an association with OS following diagnosis using univariable and multivariable analyses. Results: Nine-hundred and eighty-one patients were included (0.22% of all CNS tumors). At diagnosis, 22 patients had spinal tumors (2%), 21 patients had multifocal tumors (2%) and 28 had disseminated disease (3%). Patients either underwent surgical resection and radiation (48%), surgery alone (37%), radiation alone (6%), or biopsy alone (9%). Of patients with known extent of resection, 53% underwent gross total resection, and, of patients with known radiation modality, 15% received stereotactic radiosurgery. Among the total cohort, 3 and 10 year OS was 87% and 59%, respectively. On multivariable analysis, factors associated with inferior OS included age (HRZ1.05, p<0.001), WHO grade (p<0.001), multifocal disease (HRZ2.59, pZ0.04), disseminated disease (HRZ2.67, pZ0.01), and chemotherapy (HRZ2.66, pZ0.01). Patients receiving surgery alone or surgery and radiation demonstrated improved OS compared to biopsy alone (HRZ0.45, pZ0.01 and HRZ0.47, pZ0.02, respectively). However radiation utilization did not impact OS (pZ0.691). Conclusion: The present data provide large-scale prognostic information from a contemporary cohort of patients with hemangiopericytoma and support an initial attempt at surgical extirpation. The benefits of ionizing radiation are likely limited to improved local control and neurologic function.

To reduce the likelihood of errors in organ delineations used for radiotherapy treatment planning, a knowledge-based quality control (KBQC) system, which discriminates between valid and anomalous delineations is developed. Method and Materials:The KBQC is comprised of a group-wise inference system and anomaly detection modules trained using historical priors from 296 locally advanced lung and prostate cancer patient computational tomographies (CTs). The inference system discriminates different organs based on shape, relational, and intensity features. For a given delineated image set, the inference system solves a combinatorial optimization problem that results in an organ group whose relational features follow those of the training set considering the posterior probabilities obtained from support vector machine (SVM), discriminant subspace ensemble (DSE), and artificial neural network (ANN) classifiers. These classifiers are trained on nonrelational features with a 10-fold crossvalidation scheme. The anomaly detection module is a bank of ANN autoencoders, each corresponding with an organ, trained on nonrelational features. A heuristic rule detects anomalous organs that exceed predefined organ-specific tolerances for the feature reconstruction error and the classifier's posterior probabilities. Independent data sets with anomalous delineations were used to test the overall performance of the KBQC system. The anomalous delineations were manually manipulated, computer-generated, or propagated based on a transformation obtained by imperfect registrations. Both peer-review-based scoring system and shape similarity coefficient (DSC) were used to label regions of interest (ROIs) as normal or anomalous in two independent test cohorts. Results: The accuracy of the classifiers was ≥99.8%, and the minimum perclass F1-scores were 0.99, 0.99, and 0.98 for SVM, DSE, and ANN, respectively. The group-wise inference system reduced the miss-classification likelihood for the test data set with anomalous delineations compared to each individual classifier and a fused classifier that used the average posterior probability of all classifiers. For 15 independent locally advanced lung patients, the system detected >79% of the anomalous ROIs. For 1320 auto-segmented abdominopelvic organs, the anomaly detection system identified anomalous delineations, which also had low Dice similarity coefficient values with respect to manually delineated organs in the training data set. Conclusion:The KBQC system detected anomalous delineations with superior accuracy compared to classification methods that judge only based on posterior probabilities.

Early‐stage nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) is associated with a favorable prognosis. Our aim was to evaluate the patterns of care of radiotherapy utilization in this disease and to define the relationship between treatment modality and survival. The National Cancer Database was queried for patients with stages I‐II NLPHL diagnosed from 2004 to 2012. Patients were compared based on primary therapy into four categories: radiotherapy, chemotherapy, both, or neither. Covariate‐adjusted and propensity score‐weighted (PS) Cox proportional hazards models were used, adjusting for potential factors confounding survival. After exclusions, 1420 patients were evaluated, 571 (40%) received radiotherapy alone, 318 (22%) received chemotherapy alone, 351 (25%) received both, and 180 (13%) received neither. Younger patient age (P = 0.001), female gender (P = 0.019), and chemotherapy use (P < 0.001) were associated with decreased radiotherapy utilization. On PS, radiation alone (HR = 0.298, P < 0.001) and chemoradiotherapy (HR = 0.258, P < 0.001) were associated with improved survival compared to no upfront therapy, but the use of chemotherapy alone did not statistically differ compared to no initial therapy (HR = 0.784, P = 0.078). In this large database analysis, over one‐third of patients with early‐stage NLPHL did not receive radiotherapy as a component of initial therapy. The omission of upfront radiotherapy was associated with inferior survival.

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