Computed Tomography-Based Radiomics for Long-Term Prognostication of High-Risk Localized Prostate Cancer Patients Received Whole Pelvic Radiotherapy.

Given the high death rate caused by high-risk prostate cancer (PCa) (>40%) and the reliability issues associated with traditional prognostic markers, the purpose of this study is to investigate planning computed tomography (pCT)-based radiomics for the long-term prognostication of high-risk localized PCa patients who received whole pelvic radiotherapy (WPRT). This is a retrospective study with methods based on best practice procedures for radiomics research. Sixty-four patients were selected and randomly assigned to training (n = 45) and testing (n = 19) cohorts for radiomics model development with five major steps: pCT image acquisition using a Philips Big Bore CT simulator; multiple manual segmentations of clinical target volume for the prostate (CTVprostate) on the pCT images; feature extraction from the CTVprostate using PyRadiomics; feature selection for overfitting avoidance; and model development with three-fold cross-validation. The radiomics model and signature performances were evaluated based on the area under the receiver operating characteristic curve (AUC) as well as accuracy, sensitivity and specificity. This study's results show that our pCT-based radiomics model was able to predict the six-year progression-free survival of the high-risk localized PCa patients who received the WPRT with highly consistent performances (mean AUC: 0.76 (training) and 0.71 (testing)). These are comparable to findings of other similar studies including those using magnetic resonance imaging (MRI)-based radiomics. The accuracy, sensitivity and specificity of our radiomics signature that consisted of two texture features were 0.778, 0.833 and 0.556 (training) and 0.842, 0.867 and 0.750 (testing), respectively. Since CT is more readily available than MRI and is the standard-of-care modality for PCa WPRT planning, pCT-based radiomics could be used as a routine non-invasive approach to the prognostic prediction of WPRT treatment outcomes in high-risk localized PCa.

Effect of Time-Restricted Eating on Weight Loss in Adults With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Time-restricted eating (TRE) has become increasingly popular, yet longer-term randomized clinical trials have not evaluated its efficacy and safety in patients with type 2 diabetes (T2D). Objective: To determine whether TRE is more effective for weight reduction and glycemic control than daily calorie restriction (CR) or a control condition in adults with T2D. Design, Setting, and Participants: This 6-month, parallel-group, randomized clinical trial was performed between January 25, 2022, and April 1, 2023, at the University of Illinois Chicago. Participants were aged 18 to 80 years with obesity and T2D. Data analysis was based on intention to treat. Interventions: Participants were randomized to 1 of 3 groups: 8-hour TRE (eating 12 to 8 pm only, without calorie counting), CR (25% energy restriction daily), or control. Main Outcomes and Measures: The primary outcome measure was change in body weight by month 6. Secondary outcomes included changes in hemoglobin A1c (HbA1c) levels and metabolic risk factors. Results: Seventy-five participants were enrolled with a mean (SD) age of 55 (12) years. The mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39 (7) and the mean (SD) HbA1c level was 8.1% (1.6%). A total of 53 participants (71%) were women. One participant (1%) was Asian, 30 (40%) were Hispanic White, 40 (53%) were non-Hispanic Black, and 4 (5%) were non-Hispanic White. Participants in the TRE group were adherent with their eating window on a mean (SD) of 6.1 (0.8) days per week, and 17 (68%) in the CR group were adherent with their prescribed calorie goals over 6 months. The mean (SD) reduction in energy intake was -313 (509) kcal/d for TRE, -197 (426) kcal/d for CR, and -16 (439) kcal/d for controls. By month 6, body weight decreased significantly in the TRE group (-3.56% [95% CI, -5.92% to -1.20%]; P = .004) but not the CR group (-1.78% [95% CI, -3.67% to 0.11%]; P = .06), relative to controls. Levels of HbA1c decreased in the TRE (-0.91% [95% CI, -1.61% to -0.20%]) and CR (-0.94% [95% CI, -1.59% to -0.30%]) groups, relative to controls, with no differences between the TRE and CR groups. Time in euglycemic range, medication effect score, blood pressure, and plasma lipid levels did not differ among groups. No serious adverse events were reported. Conclusions and relevance: This randomized clinical trial found that a TRE diet strategy without calorie counting was effective for weight loss and lowering of HbA1c levels compared with daily calorie counting in a sample of adults with T2D. These findings will need to be confirmed by larger RCTs with longer follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT05225337.

Time-Restricted Eating Without Calorie Counting for Weight Loss in a Racially Diverse Population : A Randomized Controlled Trial.

BACKGROUND: Time-restricted eating (TRE), without calorie counting, has become a popular weight loss strategy, yet long-term randomized trials evaluating its efficacy are limited. OBJECTIVE: To determine whether TRE is more effective for weight control and cardiometabolic risk reduction compared with calorie restriction (CR) or control. DESIGN: 12-month randomized controlled trial. (ClinicalTrials.gov: NCT04692532). SETTING: University of Illinois Chicago from January 2021 to September 2022. PARTICIPANTS: 90 adults with obesity. INTERVENTION: 8-hour TRE (eating between noon and 8:00 p.m. only, without calorie counting), CR (25% energy restriction daily), or control (eating over a period of 10 or more hours per day). Participants were not blinded. MEASUREMENTS: Change in body weight, metabolic markers, and energy intake by month 12. RESULTS: Seventy-seven persons completed the study. Mean age was 40 years (SD, 11), 33% were Black, and 46% were Hispanic. Mean reduction in energy intake was -425 kcal/d (SD, 531) for TRE and -405 kcal/d (SD, 712) for CR. Compared with the control group, weight loss by month 12 was -4.61 kg (95% CI, -7.37 to -1.85 kg; P ≤ 0.01) (-4.87% [CI, -7.61% to -2.13%]) for the TRE group and -5.42 kg (CI, -9.13 to -1.71 kg; P ≤ 0.01) (-5.30% [CI, -9.06% to -1.54%]) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI, -3.07 to 4.69 kg; P = 0.68]) (0.43% [CI, -3.48% to 4.34%]). LIMITATION: Not blinded, not powered to detect relatively large differences in weight loss, and lack of adjustment for multiple comparisons. CONCLUSION: Time-restricted eating is more effective in producing weight loss when compared with control but not more effective than CR in a racially diverse population. PRIMARY FUNDING SOURCE: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Benzosiloles with Crystallization-Induced Emission Enhancement of Electrochemiluminescence: Synthesis, Electrochemistry, and Crystallography.

Crystallization-induced emission enhancement (CIEE) was demonstrated for the first time for electrochemilunimescence (ECL) with two new benzosiloles. Compared with their solution, the films of the two benzosiloles gave CIEE of 24 and 16 times. The mechanism of the CIEE-ECL was examined by spooling ECL spectroscopy, X-ray crystal structure analysis, photoluminescence, and DFT calculations. This CIEE-ECL system is a complement to the well-established aggregation-induced emission enhancement (AIEE) systems. Unique intermolecular interactions are noted in the crystalline chromophore. The first heterogeneous ECL system is established for organic compounds with highly hydrophobic properties.

Synthesis of Hexahydropyridazines by [4 + 2] Cycloaddition of Donor-Acceptor Cyclobutanes and cis-Diazenes.

The GaCl3-catalyzed [4 + 2] cycloaddition between alkoxy- and aryl-activated donor-acceptor cyclobutane diesters and cis-diazene 1a (4-phenyl-1,2,4-triazoline-3,5-dione, PTAD) is disclosed. The reaction provides hexahydropyridazine derivatives as single diastereomers in good to excellent yields in most cases. The structural assignment of the cycloadduct 3b was unambiguously established by single-crystal X-ray diffraction.

Synthesis of Functionalized Tetrahydropyridines by SnCl4 -Mediated [4+2] Cycloaddition between Donor-Acceptor Cyclobutanes and Nitriles.

Cycloadditions of strained carbocycles promoted by Lewis acids are powerful methods to construct heterocyclic frameworks. In fact, the formal [3+2] cycloadditions of donor-acceptor (DA) cyclopropanes with nitriles has seen particular success in synthesis. In this work, we report on the first [4+2] cycloaddition of nitriles with DA cyclobutanes by Lewis acid activation. Tetrahydropyridine derivatives were obtained in up to 91 % yield from various aryl-activated cyclobutane diesters and aliphatic or aromatic nitriles.

A Collimator Setting Optimization Algorithm for Dual-Arc Volumetric Modulated Arc Therapy in Pancreas Stereotactic Body Radiation Therapy.

PURPOSE: To optimize collimator setting to improve dosimetric quality of pancreas volumetric modulated arc therapy plan for stereotactic body radiation therapy. MATERIALS AND METHODS: Fifty-five volumetric modulated arc therapy cases in stereotactic body radiation therapy of pancreas were retrospectively included in this study with internal review board approval. Different from the routine practice of initializing collimator settings with a template, the proposed algorithm simultaneously optimizes the collimator angles and jaw positions that are customized to the patient geometry. Specifically, this algorithm includes 2 key steps: (1) an iterative optimization algorithm via simulated annealing that generates a set of potential collimator settings from 39 cases with pancreas stereotactic body radiation therapy, and (2) a multi-leaf collimator modulation scoring system that makes the final decision of the optimal collimator settings (collimator angles and jaw positions) based on organs at risk sparing criteria. For validation, the other 16 cases with pancreas stereotactic body radiation therapy were analyzed. Two plans were generated for each validation case, with one plan optimized using the proposed algorithm (Planopt) and the other plan with the template setting (Planconv). Each plan was optimized with 2 full arcs and the same set of constraints for the same case. Dosimetric results were analyzed and compared, including target dose coverage, conformity, organs at risk maximum dose, and modulation complexity score. All results were tested by Wilcoxon signed rank tests, and the statistical significance level was set to .05. RESULTS: Both plan groups had comparable target dose coverage and mean doses of all organs at risk. However, organs at risk (stomach, duodenum, large/small bowel) maximum dose sparing (D0.1 cc and D0.03 cc) was improved in Planopt compared to Planconv. Planopt also showed lower modulation complexity score, which suggests better capability of handling complex shape and sparing organs at risk . CONCLUSIONS: The proposed collimator settings optimization algorithm successfully improved dosimetric performance for dual-arc pancreas volumetric modulated arc therapy plans in stereotactic body radiation therapy of pancreas. This algorithm has the capability of immediate clinical application.

NCTN Assessment on Current Applications of Radiomics in Oncology.

Radiomics is a fast-growing research area based on converting standard-of-care imaging into quantitative minable data and building subsequent predictive models to personalize treatment. Radiomics has been proposed as a study objective in clinical trial concepts and a potential biomarker for stratifying patients across interventional treatment arms. In recognizing the growing importance of radiomics in oncology, a group of medical physicists and clinicians from NRG Oncology reviewed the current status of the field and identified critical issues, providing a general assessment and early recommendations for incorporation in oncology studies.

Temporal lobe injury patterns following intensity modulated radiotherapy in a large cohort of nasopharyngeal carcinoma patients.

OBJECTIVES: To analyze the correlation between dose-volume-histograms (DVHs) with three patterns (edema, enhancement, and necrosis) of temporal lobe injury (TLI) in patients receiving intensity modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine optimal thresholds to predict the incidence of each TLI pattern, with particular emphasis on the relationship between edema volume and the risk of enhancement and necrosis. MATERIALS AND METHODS: A cohort of 4186 NPC patients treated with IMRT was retrospectively reviewed with TLI presenting in 188 patients. The atlases of complication incidence (ACI) for each pattern were constructed using DVH curves of temporal lobes. Optimal threshold for predicting incidence of each pattern was determined using the point closest to top-left of the plot. The accuracy of using edema volume to predict enhancement and necrosis incidence was evaluated via area under curve (AUC) of receiver operator characteristics (ROC). RESULTS: All DVH parameters, Dmean, Dmax, D0.25cc, D0.5cc, D1cc, D3cc, D6cc, V20Gy, V30Gy, V40Gy, V50Gy, V60Gy, and V70Gy, except Dmin showed statistically significant differences between subgroups of each pattern (p < 0.05). For predicting incidence of each pattern, optimal DVH thresholds over the range of D0.25-D1cc, Dmean and V20-V70 were derived. The optimal thresholds of edema volume for predicting enhancement were 0.96 and 2.2cc and for predicting necrosis were 0.94 and 11.5cc. CONCLUSION: Optimal DVH thresholds were generated for limiting risk of each injury pattern. Edema volume was a strong predictor for risk of enhancement and necrosis, which could potentially be reduced by lowering edema volume below threshold.

Colonoscopy procedure simulation: virtual reality training based on a real time computational approach.

BACKGROUND: Colonoscopy plays an important role in the clinical screening and management of colorectal cancer. The traditional 'see one, do one, teach one' training style for such invasive procedure is resource intensive and ineffective. Given that colonoscopy is difficult, and time-consuming to master, the use of virtual reality simulators to train gastroenterologists in colonoscopy operations offers a promising alternative. METHODS: In this paper, a realistic and real-time interactive simulator for training colonoscopy procedure is presented, which can even include polypectomy simulation. Our approach models the colonoscopy as thick flexible elastic rods with different resolutions which are dynamically adaptive to the curvature of the colon. More material characteristics of this deformable material are integrated into our discrete model to realistically simulate the behavior of the colonoscope. CONCLUSION: We present a simulator for training colonoscopy procedure. In addition, we propose a set of key aspects of our simulator that give fast, high fidelity feedback to trainees. We also conducted an initial validation of this colonoscopic simulator to determine its clinical utility and efficacy.

Toxicity and quality of life report of a phase II study of stereotactic body radiotherapy (SBRT) for low and intermediate risk prostate cancer.

BACKGROUND: Clinical data indicates that delivery of larger daily doses of radiation may improve the therapeutic ratio for prostate cancer compared to conventional fractionation. A phase II study of stereotactic body radiotherapy with real-time motion management and daily plan re-optimization for low to intermediate risk prostate cancer was undertaken to evaluate this hypothesis. This report details the toxicity and quality of life following treatment. METHODS: From 2009 to 2013, 60 patients with T1-T2c prostate cancer with a Gleason score of 6 and PSA ≤ 15 or Gleason score of 7 and PSA ≤ 10 were enrolled. Patients with nodal metastases, an American Urological Association symptom score > 18, or gland size > 100 g were not eligible. Patients were treated to 37 Gy in 5 fractions. Early and late genitourinary and gastrointestinal toxicity were graded based on NCI CTCAE v4.0 and quality of life was assessed by the American Urological Association symptom score, International Index of Erectile Function, and Expanded Prostate cancer Index Composite Short Form up to 36 months after treatment. RESULTS: After a median follow-up of 27.6 months, no grade 3 or greater genitourinary toxicity was observed. Four patients (6.7%) reported a late grade 2 genitourinary toxicity. One patient (1.7%) reported a late grade 3 gastrointestinal toxicity. Five patients (8.3%) developed a late grade 2 gastrointestinal toxicity. The median American Urological Association symptom score increased from 4.5 prior to treatment to 11 while on treatment (p < 0.01), but was 5 at 36 months post-treatment (p = 0.65). Median International Index of Erectile Function scores decreased from 19 to 17 over the course of follow-up (p < 0.01). Only median scores within the Expanded Prostate Cancer Index Composite Short Form sexual domain were significantly decreased at 36 months post-treatment (67.9 vs 45.2, p = 0.02). There was no significant difference in median score within the urinary, bowel, or hormonal domains at 36 months of follow-up. CONCLUSIONS: Stereotactic body radiotherapy for low to intermediate risk prostate cancer is well tolerated with limited toxicity or decrease in quality of life. Longer follow-up is necessary to assess the efficacy of treatment. TRIAL REGISTRATION: Clinicaltrials.gov NCT00941915 Registered 17 June 2009.

3D-resolved targeting of photodynamic therapy using temporal focusing.

A method for selectively inducing apoptosis in tumor nodules is presented, with close-to-cellular level resolution, using 3D-resolved widefield temporal focusing illumination. Treatment times on the order of seconds were achieved using Verteporfin as the photosensitizer, with doses of 30 µg ml-1 and below. Results were achieved on both 2D and 3D cell cultures, demonstrating that treatment was possible through approximately one hundred microns of dense tumor nodules.

Evaluation of Image Enhancement Method on Target Registration Using Cone Beam CT in Radiation Therapy.

An intensity based six-degree image registration algorithm between cone-beam CT (CBCT) and planning CT has been developed for image-guided radiation therapy (IGRT). CT images of an anthropomorphic chest phantom were acquired using conventional CT scanner and corresponding CBCT was reconstructed based on projection images acquired by an on-board imager (OBI). Both sets of images were initially registered to each other using attached fudicial markers to achieve a golden standard registration. Starting from this point, an offset was applied to one set of images, and the matching result was found by a gray-value based registration method. Finally, The registration error was evaluated by comparing the detected shifts with the known shift. Three window-level (WL) combinations commonly used for image enhancement were examined to investigate the effect of anatomical information of Bony only (B), Bone+Tissue (BT), and Bone+Tissue+Air (BTA) on the accuracy and robustness of gray-value based registration algorithm. Extensive tests were performed in searching for the attraction range of registration algorithm. The widest attraction range was achieved with the WL combination of BTA. The average attraction ranges of this combination were 73.3 mm and 81.6 degree in the translation and rotation dimensions, respectively, and the average registration errors were 0.15 mm and 0.32 degree. The WL combination of BT shows the secondary largest attraction ranges. The WL combination of B shows limited convergence property and its attraction range was the smallest among the three examined combinations (on average 33.3 mm and 25.0 degree). If two sets of 3D images in original size (512 × 512) were used, registration could be accomplished within 10~20 minutes by current algorithm, which is only acceptable for off-line reviewing purpose. As the size of image set reduced by a factor of 2~4, the registration time would be 2~4 minutes which is feasible for on-line target localization.

Plug pattern optimization for gamma knife radiosurgery treatment planning.

PURPOSE: To develop a novel dose optimization algorithm for improving the sparing of critical structures during gamma knife radiosurgery by shaping the plug pattern of each individual shot. METHOD AND MATERIALS: We first use a geometric information (medial axis) aided guided evolutionary simulated annealing (GESA) optimization algorithm to determine the number of shots and isocenter location, size, and weight of each shot. Then we create a plug quality score system that checks the dose contribution to the volume of interest by each plug in the treatment plan. A positive score implies that the corresponding source could be open to improve tumor coverage, whereas a negative score means the source could be blocked for the purpose of sparing normal and critical structures. The plug pattern is then optimized via the GESA algorithm that is integrated with this score system. Weight and position of each shot are also tuned in this procedure. RESULTS: An acoustic tumor case is used to evaluate our algorithm. Compared to the treatment plan generated without plug patterns, adding an optimized plug pattern into the treatment planning process boosts tumor coverage index from 95.1% to 97.2%, reduces RTOG conformity index from 1.279 to 1.167, lowers Paddick's index from 1.34 to 1.20, and trims the critical structure receiving more than 30% maximum dose from 16 mm(3) to 6 mm(3). CONCLUSIONS: Automated GESA-based plug pattern optimization of gamma knife radiosurgery frees the treatment planning team from the manual forward planning procedure and provides an optimal treatment plan.

Implementation of the isocenter-shift technique for smoothing MLC field edge on a 3D treatment planning system.

Stepped leaf edges are the major limitation of conforming to the prescribed treatment contour defined by the conventional multileaf collimator (MLC), which produces a scalloped dose pattern. The commercial HD-270 MLC (HDI) technique provides a software solution of the conventional MLC to achieve smoothed edge and optimal penumbra of the MLC shaped field. We implemented the HDI functionality on a 3D treatment planning system and compared the dosimetric effects of the HDI delivery in simulation with those in experiment for a number of the MLC fields. The fields from the contour of varied shapes with different sizes of the leaf stepping were tested for the HDI delivery. There is a good agreement of the dose distribution between the calculation as implemented in the planning system and the measurement performed on the treatment machine. It has been shown that the HDI delivery significantly smooths the stepped field edge with the reduced isodose undulation and effective penumbra. A problem may be present when the HDI is applied for the treatment of the circular contour of smaller diameter, and the conformity of the MLC shaping may not be achievable satisfactorily with the existing system. The optimization of leaf configuration is suggested to improve the conformity of the HDI technique. The HDI planning then can be used to assist in the decision making of applying the HDI treatment delivery.