Contrast-Enhanced Liver Magnetic Resonance Image Synthesis Using Gradient Regularized Multi-Modal Multi-Discrimination Sparse Attention Fusion GAN.

PURPOSES: To provide abdominal contrast-enhanced MR image synthesis, we developed an gradient regularized multi-modal multi-discrimination sparse attention fusion generative adversarial network (GRMM-GAN) to avoid repeated contrast injections to patients and facilitate adaptive monitoring. METHODS: With IRB approval, 165 abdominal MR studies from 61 liver cancer patients were retrospectively solicited from our institutional database. Each study included T2, T1 pre-contrast (T1pre), and T1 contrast-enhanced (T1ce) images. The GRMM-GAN synthesis pipeline consists of a sparse attention fusion network, an image gradient regularizer (GR), and a generative adversarial network with multi-discrimination. The studies were randomly divided into 115 for training, 20 for validation, and 30 for testing. The two pre-contrast MR modalities, T2 and T1pre images, were adopted as inputs in the training phase. The T1ce image at the portal venous phase was used as an output. The synthesized T1ce images were compared with the ground truth T1ce images. The evaluation metrics include peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and mean squared error (MSE). A Turing test and experts' contours evaluated the image synthesis quality. RESULTS: The proposed GRMM-GAN model achieved a PSNR of 28.56, an SSIM of 0.869, and an MSE of 83.27. The proposed model showed statistically significant improvements in all metrics tested with p-values < 0.05 over the state-of-the-art model comparisons. The average Turing test score was 52.33%, which is close to random guessing, supporting the model's effectiveness for clinical application. In the tumor-specific region analysis, the average tumor contrast-to-noise ratio (CNR) of the synthesized MR images was not statistically significant from the real MR images. The average DICE from real vs. synthetic images was 0.90 compared to the inter-operator DICE of 0.91. CONCLUSION: We demonstrated the function of a novel multi-modal MR image synthesis neural network GRMM-GAN for T1ce MR synthesis based on pre-contrast T1 and T2 MR images. GRMM-GAN shows promise for avoiding repeated contrast injections during radiation therapy treatment.

Knowledge and Understanding of Radiation Therapy Among Patients With Breast Cancer From Culturally Diverse Backgrounds at a Safety-Net Hospital.

INTRODUCTION: Comprehensive understanding of oncologic treatment is essential for shared decision-making. However, comprehension of information in radiation oncology consults is poorly understood, particularly among Spanish-speaking patients at safetynet hospitals. The purpose of this pilot study was to examine post-consultation radiation oncology knowledge and health literacy among breast cancer patients from culturally diverse backgrounds. METHODS: After consultation for curative post-operative breast radiotherapy (cT1-4N1-3M0), the Radiation Oncology Knowledge Assessment Survey (ROKAS) was administered to Spanish- and English-speaking patients ≥ 18 years old, from January 2021 to January 2022 at a safety-net hospital. Radiation knowledge was assessed using the ROKAS which included eight radiation-specific multiple-choice questions and two separate questions regarding short- and long-term side effects. Additional independent variables included validated questionnaires related to health literacy, health numeracy, acculturation, primary language, and sociodemographic factors. Bivariate Pearson correlations and T-test analyses were conducted to examine the relationship between the independent variables and post-consultation radiation knowledge. RESULTS: Fifty ROKAS were obtained from 25 English- and 25 Spanish-speaking breast cancer patients (median age 57 [IQR 49.75-62.25]). When compared to Englishspeaking patients, Spanish-speaking patients had lower health literacy, health numeracy, and acculturation. There was no difference in the multiple-choice ROKAS score between English- and Spanish-speakers, or correlation with the other independent factors. Higher health numeracy correlated with a higher accuracy for identifying short-term side effects. Lower accuracy of identifying long-term side effects was seen in patients with lower education levels, health literacy, health numeracy, and acculturation, with the most missed long-term side effects being arm swelling, skin toxicity, and heart toxicity. CONCLUSIONS: Patients with low health literacy, health numeracy, acculturation, and education levels as well as Spanish-speaking patients were associated with poor understanding of radiotherapy long-term side effects. Determining barriers to radiation knowledge is crucial to improve shared decision-making between patients and providers in a culturally diverse population.

Combining Immunotherapy with Radiotherapy for the Treatment of Genitourinary Malignancies.

CONTEXT: Immunotherapy drugs, particularly checkpoint inhibitors, have recently been approved by the Food and Drug Administration for various malignancies. Preclinical and early clinical data show that combining these agents with radiotherapy may produce an even more potent antitumor effect in the treatment of cancer. OBJECTIVE: To describe the rationale, available data, and emerging data on the use of combined immunotherapy and radiation therapy in the setting of genitourinary (GU) malignancies. EVIDENCE ACQUISITION: We performed a search of primary studies from PubMed/Medline that included combinations of the search terms "radiation therapy," "radiotherapy," "abscopal effect," "immunotherapy," "combined," and "combination." EVIDENCE SYNTHESIS: Preclinical and clinical data support both immune-stimulating and immune-suppressing effects of radiotherapy. Preclinical and clinical studies investigating the combination of radiotherapy with immunotherapy, primarily in the setting of non-GU malignancies, have suggested efficacy and tolerability. Early randomized trials combining radiotherapy and immunotherapy have demonstrated success in lung cancer. Although a trial investigating combined immunotherapy and radiotherapy use for prostate cancer did not clearly improve survival, trials are ongoing in multiple GU malignancies to identify synergy between immunotherapy and radiotherapy. Several practical and technical questions remain about the optimal combination of radiotherapy and immunotherapy. CONCLUSIONS: Preclinical and clinical trials show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating cancer, including GU malignancies, although more work is needed to uncover the mechanism and determine the optimal delivery of this treatment. PATIENT SUMMARY: This paper reviews evidence that immunotherapy drugs can be given together with radiation therapy to improve outcomes in cancers of the genitourinary tract. We find promising initial results and raise important questions that need to be answered before this type of treatment can be utilized successfully.

Predictors of breast cancer mortality among white and black women in large United States cities: an ecologic study.

PURPOSE: We employed a city-level ecologic analysis to assess predictors of race-specific (black and white) breast cancer mortality rates. METHODS: We used data from the National Center for Health Statistics and the US Census Bureau to calculate 2010-2014 race-specific breast cancer mortality rates (BCMR) for 47 of the largest US cities. Data on potential city-level predictors (e.g., socioeconomic factors, health care resources) of race-specific BCMR were obtained from various publicly available datasets. We constructed race-specific multivariable negative binomial regression models to estimate rate ratios (RR) and 95% confidence intervals (CIs). RESULTS: Predictors of the white BCMR included white/black differences in education (RR 0.95; CI 0.91-0.99), number of religious congregations (RR 0.87; CI 0.77-0.97), and number of Medicare primary care physicians (RR 1.15; CI 1.04-1.28). Predictors of the black rate included white/black differences in household income (RR 1.03; CI 1.01-1.05), number of mammography facilities (RR 1.07; CI 1.03-1.12), and mammogram use (RR 0.93; CI 0.89-0.97). CONCLUSIONS: Our ecologic analysis found that predictors of breast cancer mortality differ for the black and white rate. The results of this analysis could help inform interventions at the local level.

Postoperative stereotactic radiosurgery for patients with resected brain metastases: a volumetric analysis.

PURPOSE: Postoperative stereotactic radiosurgery (SRS) is increasingly utilized following resection of brain metastases (BM); however, there are no volumetric data guiding dose selection. We performed a volumetric analysis to guide cavity SRS dosing for resected BM. METHODS: 83 consecutive patients with gross total resection who underwent postoperative SRS to 90 cavities were identified. The 12 Gy isodose lines (V12total) along with the volume of brain parenchyma receiving 12 Gy excluding cavity fluid, ventricular fluid, and calvarium (V12parenchyma) were contoured. Local recurrence (LR) and radionecrosis (RN) were calculated using cumulative incidence rates. Multivariate analysis (MVA) and cutpoint analysis were conducted. RESULTS: Median follow-up was 12.3 months; median dose was 16 Gy. 1- and 2-year cumulative incidence rates of LR were 7.9% and 11.0%. Radiation dose [hazard ratio (HR) 2.04, p = 0.002] was significantly associated with time to LR on MVA. 1- and 2-year cumulative incidence rates of RN were 2.6% and 5.5% respectively. MVA demonstrated increased risk of RN with a larger V12parenchyma (HR 1.46, p = 0.0496). Cavities ≤ 10 cc showed a low 2-year RN risk (4.3%), but had a modest LR risk (13.9%). A radiation dose ≥ 18 Gy significantly improved LC (HR 4.79, p = 0.01). CONCLUSIONS: V12parenchyma should be examined in postoperative SRS to assess RN risk. Cavities > 10 cc treated with 16 Gy achieved excellent LC and minimal RN at 2 years. Cavities ≤ 10 cc may be better treated with a dose ≥ 18 Gy to significantly improve LC given the low RN rate observed with 16 Gy.

Postsurgical Cavity Evolution After Brain Metastasis Resection: How Soon Should Postoperative Radiosurgery Follow?

BACKGROUND: Postoperative stereotactic radiosurgery (SRS) to the cavity after resection of brain metastases improves local control. We hypothesized that significant cavity constriction would occur from the immediate postoperative period to the time of SRS and aimed to elucidate optimal treatment timing. METHODS: We retrospectively reviewed 79 consecutive patients with 85 resection cavities treated with SRS after gross total resection of a brain metastasis. Preoperative lesion, immediate postoperative cavity, and cavity at the time of SRS were contoured for each patient. Factors influencing cavity size and interval cavity change were analyzed. RESULTS: Median immediate postoperative cavity volume was 7.5 cm3, and median SRS cavity volume was 8.7 cm3. Median time from surgery to SRS was 20 days. Median volumetric cavity change was an increase of 28%. Of cavities, 34 (40%) increased in size >2 cm3, whereas only 8 cavities (9%) decreased in size >2 cm3; 43 cavities (51%) had ≤2 cm3 change. The largest postoperative cavities experienced the smallest percentage cavity change in the time interval to SRS (Spearman correlation -0.32, P = 0.003). CONCLUSIONS: Cavity size after brain metastasis resection increased a median of 28% from immediate postoperative scan to time of SRS. Greater than 90% of postoperative cavities either increased >2 cm3 or remained within 2 cm3 of their immediate postoperative cavity volume. Early postoperative SRS within 2-3 weeks may be appropriate to minimize cavity growth. Delaying postoperative SRS beyond 3 weeks in hopes of significant cavity contraction is not warranted.

Single Fraction Stereotactic Radiosurgery for Retreatment of Skull Base Recurrent Head and Neck Malignancies.

INTRODUCTION: Recurrent head and neck carcinomas are notoriously difficult to treat. Salvage surgery, brachytherapy, and repeat external beam radiotherapy have all been utilized, achieving modest local control at the expense of elevated toxicity. We performed a retrospective review to evaluate the efficacy of single fraction stereotactic radiosurgery (SRS) for the treatment of recurrent head and neck carcinomas. METHODS: Eighteen previously irradiated patients diagnosed with a locoregionally recurrent head and neck malignancy and treated with single fraction SRS from 2000 to 2016 were analyzed. Actuarial rates for local control (LC) and overall survival (OS) were calculated with Kaplan-Meier estimates. RESULTS: Median follow-up was 16.1 months and SRS dose was 13.3 Gy. One-year rate of LC was 52.7% (95% confidence interval [CI] 29%-72%). Median OS was 25.4 months. Parotid gland primary had an increased risk of progressive disease (PD) following SRS (hazard ratio [HR] 4.24, p=0.02). Squamous cell histology was negatively associated with OS (HR 3.85, p=0.03). One patient experienced grade 2 radionecrosis. CONCLUSIONS: Single fraction SRS is an acceptable treatment for previously irradiated patients with recurrent head and neck primary malignancies. Dose escalation to optimize LC should be examined.

Resting state and task-related brain dynamics supporting insight.

Problems can be solved in a variety of ways. One might systematically evaluate a known space of possible solutions until the right one is found. Alternatively, it may prove necessary to enlarge or restructure the expected problem space - so called "thinking outside the box." This approach can yield an experience of unexpected insight or feeling of Aha!. Current challenges to understanding this phenomenon from a neurocognitive perspective include the vast diversity of problem domains and time scales for solutions. Whereas the subjective suddenness of an "Aha!" moment may lead to the impression that insight must be precipitated by a set of discrete, short-lived neural events, this report outlines research revealing that even before a problem is presented, scalp-recorded measures of resting or baseline brain states are linked with future performance and likelihood of experiencing insight during the search for a solution. Additionally, this study also shows that compared to more systematic problem solving approaches, insight is accompanied by differences in cortical and likely cognitive engagement that are detectable throughout much of the problem solving phase, rather than being confined to a distinct interval immediately preceding the dawn of a solution. These findings are important for the development of therapies targeting problem solving and reasoning skills, such as those used in cognitive training interventions to mitigate the effects of cognitive decline.