Automated Treatment Planning and Non-coplanar Beam Angles in Radiotherapy

Automation of the treatment plan generation in radiotherapy showed to play a key role in patient care. It can highly improve plan quality, reduce planner influence, increase standardization and easily generate a high numb

Automated Radiotherapy Planning for Patient-Specific Exploration of the Trade-Off Between Tumor Dose Coverage and Predicted Radiation-Induced Toxicity-A Proof of Principle Study for Prostate Cancer

Background: Currently, radiation-oncologists generally evaluate a single treatment plan for each patient that is possibly adapted by the planner prior to final app

Complementing Prostate SBRT VMAT With a Two-Beam Non-Coplanar IMRT Class Solution to Enhance Rectum and Bladder Sparing With Minimum Increase in Treatment Time

Purpose Enhance rectum and bladder sparing in prostate SBRT with minimum increase in treatment time by complementing dual-arc coplanar VMAT with a two-beam non-coplanar IMRT class solution (CS). Methods For twenty patients, an optimizer for automated multi-criterial planning with integrated beam angle optimization (BAO) was used to generate dual-arc VMAT plans, supplemented with five non-coplanar IMRT beams with individually optimized orientations (VMAT+5). In all plan generations, reduction of high rectum dose had the highest priority after obtaining adequate PTV coverage. A CS with two most preferred directions in VMAT+5 and largest rectum dose reductions compared to dual-arc VMAT was then selected to define VMAT+CS. VMAT+CS was compared with automatically generated i) dual-arc coplanar VMAT plans (VMAT), ii) VMAT+5 plans, and iii) IMRT plans with 30 patient-specific non-coplanar beam orientations (30-NCP). Plans were generated for a 4 x 9.5 Gy fractionation scheme. Differences in PTV doses, healthy tissue sparing, and computation and treatment delivery times were quantified. Results For equal PTV coverage, VMAT+CS, consisting of dual-arc VMAT supplemented with two fixed, non-coplanar IMRT beams with fixed Gantry/Couch angles of 65 degrees/30 degrees and 295 degrees/-30 degrees, significantly reduced OAR doses and the dose bath, compared to dual-arc VMAT. Mean relative differences in rectum D-mean, D-1cc, V-40GyEq and V-60GyEq were 19.4 +/- 10.6%, 4.2 +/- 2.7%, 34.9 +/- 20.3%, and 39.7 +/- 23.2%, respectively (all p Conclusions The proposed two-beam non-coplanar class solution to complement coplanar dual-arc VMAT resulted in substantial plan quality improvements for OARs (especially rectum) and reduced irradiated patient volumes with minor increases in treatment delivery times

Stages of Change – Continuous Measure (URICA-E2): psychometrics of a Norwegian version

Aim: This paper is a report of research to translate the English version of the Stages of Change continuous measure questionnaire (URICA‐E2) into Norwegian and to test the validity of the questionnaire and its usefulness in predicting behavioural change. Background: While the psychometric properties of the Stages of Change categorical measure have been tested extensively, evaluation of the psychometric properties of the continuous questionnaire has not been described elsewhere in the literature. Method: Cross‐sectional data were collected with a convenience sample of 198 undergraduate nursing students in 2005 and 2006. The English version of URICA‐E2 was translated into Norwegian according to standardized procedures. Findings: Principal components analysis clearly confirmed five of the dimensions of readiness to change (Precontemplation Non‐Believers, Precontemplation Believers, Contemplation, Preparation and Maintenance), while the sixth dimension, Action, showed the lowest Eigenvalue (0·93). Findings from the cluster analysis indicate distinct profiles among the respondents in terms of readiness to change their exercise behaviour. Conclusion: The URICA‐E2 was for the most part replicated from Reed’s original work. The result of the cluster analysis of the items associated with the factor ‘Action’ suggests that these do not adequately measure the factor

The Role of the Insulin/IGF System in Cancer: Lessons Learned from Clinical Trials and the Energy Balance-Cancer Link

Numerous epidemiological and pre-clinical studies have demonstrated that the insulin/insulin-like growth factor (IGF) system plays a key role in the development and progression of several types of cancer. Insulin/IGF signaling, in cooperation with chronic low-grade inflammation, is also an important contributor to the cancer-promoting effects of obesity. However, clinical trials for drugs targeting different components of this system have produced largely disappointing results, possibly due to the lack of predictive biomarker use and problems with the design of combination therapy regimens. With careful attention to the identification of likely patient responders and optimal drug combinations, the outcome of future trials may be improved. Given that insulin/IGF signaling is known to contribute to obesity-associated cancer, further investigation regarding the efficacy of drugs targeting this system and its downstream effectors in the obese patient population is warranted

Individualized automated planning for dose bath reduction in robotic radiosurgery for benign tumors

Object To explore the use of automated planning in robotic radiosurgery of benign vestibular schwannoma (VS) tumors for dose reduction outside the planning target volume (PTV) to potentially reduce risk of secondary tumor induction. Methods A system for automated planning (AUTOplans) for VS patients was set up. The goal of AUTO- planning was to reduce the dose bath, including the occurrence of high dose spikes leaking from the PTV into normal tissues, without worsening PTV coverage, OAR doses, or treatment time. For 20 VS patients treated with 1x12 Gy, the AUTOplan was compared with the plan generated with conventional, manual trial-and-error planning (MANplan). Results With equal PTV coverage, AUTOplans showed clinically negligible differences with MANplans in OAR sparing (largest mean difference for all OARs: ΔD2% = 0.2 Gy). AUTOplan dose distributions were more compact: mean/maximum reductions of 23.6/53.8% and 9.6/ 28.5% in patient volumes receiving more than 1 or 6 Gy, respectively (p<0.001). AUTOplans also showed smaller dose spikes with mean/maximum reductions of 22.8/37.2% and 14.2/ 40.4% in D2% for shells at 1 and 7 cm distance from the PTV, respectively (p<0.001). Conclusion Automated planning for benign VS tumors highly outperformed manual planning with respect to the dose bath outside the PTV, without deteriorating PTV coverage or OAR sparing, or significantly increasing treatment time

Obesity Suppresses Estrogen Receptor Beta Expression in Breast Cancer Cells via a HER2-Mediated Pathway

Obesity is associated with a worse breast cancer prognosis, while greater breast tumor estrogen receptor beta (ERβ) expression is correlated with improved therapy response and survival. The objective of this study was to determine the impact of obesity on breast cancer cell ERβ expression, which is currently unknown. We utilized an in vitro model of obesity in which breast cancer cells were exposed to patient serum pooled by body mass index category (obese (OB): ≥30 kg/m2; normal weight (N): 18.5–24.9 kg/m2). Four human mammary tumor cell lines representing the major breast cancer subtypes (SKBR3, MCF-7, ZR75, MDA-MB-231) and mammary tumor cells from MMTV-neu mice were used. ERβ expression, assessed by qPCR and western blotting, was suppressed in the two HER2-overexpressing cell lines (SKBR3, MMTV-neu) following OB versus N sera exposure, but did not vary in the other cell lines. Expression of Bcl-2 and cyclin D1, two genes negatively regulated by ERβ, was elevated in SKBR3 cells following exposure to OB versus N sera, but this difference was eliminated when the ERβ gene was silenced with siRNA. Herceptin, a HER2 antagonist, and siRNA to HER2 were used to evaluate the role of HER2 in sera-induced ERβ modulation. SKBR3 cell treatment with OB sera plus Herceptin increased ERβ expression three-fold. Similar results were obtained when HER2 expression was silenced with siRNA. OB sera also promoted greater SKBR3 cell viability and growth, but this variance was not present when ERβ was silenced or the cells were modified to overexpress ERβ. Based on this data, we conclude that obesity-associated systemic factors suppress ERβ expression in breast cancer cells via a HER2-mediated pathway, leading to greater cell viability and growth. Elucidation of the mechanism(s) mediating this effect could provide important insights into how ERβ expression is regulated as well as how obesity promotes a more aggressive disease

A Tribute to the Mind, Methodology and Mentoring of Wayne Velicer

Wayne Velicer is remembered for a mind where mathematical concepts and calculations intrigued him, behavioral science beckoned him, and people fascinated him. Born in Green Bay, Wisconsin on March 4, 1944, he was raised on a farm, although early influences extended far beyond that beginning. His Mathematics BS and Psychology minor at Wisconsin State University in Oshkosh, and his PhD in Quantitative Psychology from Purdue led him to a fruitful and far-reaching career. He was honored several times as a high-impact author, was a renowned scholar in quantitative and health psychology, and had more than 300 scholarly publications and 54,000+ citations of his work, advancing the arenas of quantitative methodology and behavioral health. In his methodological work, Velicer sought out ways to measure, synthesize, categorize, and assess people and constructs across behaviors and time, largely through principal components analysis, time series, and cluster analysis. Further, he and several colleagues developed a method called Testing Theory-based Quantitative Predictions, successfully applied to predicting outcomes and effect sizes in smoking cessation, diet behavior, and sun protection, with the potential for wider applications. With $60,000,000 in external funding, Velicer also helped engage a large cadre of students and other colleagues to study methodological models for a myriad of health behaviors in a widely applied Transtheoretical Model of Change. Unwittingly, he has engendered indelible memories and gratitude to all who crossed his path. Although Wayne Velicer left this world on October 15, 2017 after battling an aggressive cancer, he is still very present among us

First system for fully-automated multi-criterial treatment planning for a high-magnetic field MR-Linac applied to rectal cancer

Background and purpose: In this study we developed a workflow for fully-automated generation of deliverable IMRT plans for a 1.5 T MR-Linac (MRL) based on contoured CT scans, and we evaluated automated MRL planning for rectal cancer. Methods: The Monte Carlo dose calculation engine used in the clinical MRL TPS (Monaco, Elekta AB, Stockholm, Sweden), suited for high accuracy dose calculations in a 1.5 T magnetic field, was coupled to our in-house developed Erasmus-iCycle optimizer. Clinically deliverable plans for 23 rectal cancer patients were automatically generated in a two-step process, i.e., multi-criterial fluence map optimization with Erasmus-iCycle followed by a conversion into a deliverable IMRT plan in the clinical TPS. Automatically generated plans (AUTOplans) were compared to plans that were manually generated with the clinical TPS (MANplans). Results: With AUTOplanning large reductions in planning time and workload were obtained; 4–6 h mainly hands-on planning for MANplans vs 1 h of mainly computer computation time for AUTOplans. For equal target coverage, the bladder and bowel bag Dmean was reduced in the AUTOplans by 1.3 Gy (6.9%) on average with a maximum reduction of 4.5 Gy (23.8%). Dosimetric measurements at the MRL demonstrated clinically acceptable delivery accuracy for the AUTOplans. Conclusions: A system for fully automated multi-criterial planning for a 1.5 T MR-Linac was developed and tested for rectal cancer patients. Automated planning resulted in major reductions in planning workload and time, while plan quality improved. Negative impact of the high magnetic field on the dose distributions could be avoided

Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank\u27s contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies