Assessment of treatment response to dendritic cell vaccine in patients with glioblastoma using a multiparametric MRI-based prediction model.

PURPOSE: Autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) is a promising treatment modality for glioblastomas. The purpose of this study was to investigate the potential utility of multiparametric MRI-based prediction model in evaluating treatment response in glioblastoma patients treated with DCVax-L. METHODS: Seventeen glioblastoma patients treated with standard-of-care therapy + DCVax-L were included. When tumor progression (TP) was suspected and repeat surgery was being contemplated, we sought to ascertain the number of cases correctly classified as TP + mixed response or pseudoprogression (PsP) from multiparametric MRI-based prediction model using histopathology/mRANO criteria as ground truth. Multiparametric MRI model consisted of predictive probabilities (PP) of tumor progression computed from diffusion and perfusion MRI-derived parameters. A comparison of overall survival (OS) was performed between patients treated with standard-of-care therapy + DCVax-L and standard-of-care therapy alone (external controls). Additionally, Kaplan-Meier analyses were performed to compare OS between two groups of patients using PsP, Ki-67, and MGMT promoter methylation status as stratification variables. RESULTS: Multiparametric MRI model correctly predicted TP + mixed response in 72.7% of cases (8/11) and PsP in 83.3% (5/6) with an overall concordance rate of 76.5% with final diagnosis as determined by histopathology/mRANO criteria. There was a significant concordant correlation coefficient between PP values and histopathology/mRANO criteria (r = 0.54; p = 0.026). DCVax-L-treated patients had significantly prolonged OS than those treated with standard-of-care therapy (22.38 ± 12.8 vs. 13.8 ± 9.5 months, p = 0.040). Additionally, glioblastomas with PsP, MGMT promoter methylation status, and Ki-67 values below median had longer OS than their counterparts. CONCLUSION: Multiparametric MRI-based prediction model can assess treatment response to DCVax-L in patients with glioblastoma.

Multiparametric MRI assessment of response to convection-enhanced intratumoral delivery of MDNA55, an interleukin-4 receptor targeted immunotherapy, for recurrent glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor and carries a dismal prognosis. Attempts to develop biologically targeted therapies are challenging as the blood-brain barrier can limit drugs from reaching their target when administered through conventional (intravenous or oral) routes. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. To circumvent these problems, convection-enhanced delivery (CED) provides direct, targeted, intralesional therapy with a secondary objective to alter the tumor microenvironment from an immunologically "cold" (nonresponsive) to an "inflamed" (immunoresponsive) tumor. CASE DESCRIPTION: We report a patient with right occipital recurrent GBM harboring poor prognostic genotypes who was treated with MRI-guided CED of a fusion protein MDNA55 (a targeted toxin directed toward the interleukin-4 receptor). The patient underwent serial anatomical, diffusion, and perfusion MRI scans before initiation of targeted therapy and at 1, 3-month posttherapy. Increased mean diffusivity along with decreased fractional anisotropy and maximum relative cerebral blood volume was noted at follow-up periods relative to baseline. CONCLUSION: Our findings suggest that diffusion and perfusion MRI techniques may be useful in evaluating early response to CED of MDNA55 in recurrent GBM patients.

Effects of baby-friendly practices on breastfeeding duration in China: a case-control study.

BACKGROUND: The Baby-Friendly Hospital Initiative is generally considered an effective way to promote breastfeeding. Although China has the largest number of baby-friendly hospitals in the world, research on baby-friendly practices in China is limited, and the rate of exclusive breastfeeding (EBF) at 6 months, 20.7%, compared to the 2025 global goal of 50% is low. It is, therefore, important to determine the factors that remain significant barriers to EBF in China. To explore how the key baby-friendly practices affect EBF duration in China, we used a case-control study to compare the effects of baby-friendly-related practices on both EBF and non-breastfeeding (NBF) mothers at 3 months and to investigate the effects of both single and comprehensive baby-friendly practices in promoting EBF duration at 3 months, which is one step toward EBF at 6 months. METHODS: Participants were recruited from four maternal and child health hospitals in western (Chongqing), eastern (Qingdao), southern (Liuzhou), and central China (Maanshan). A total of 421 mothers (245 in the EBF group, 176 in the NBF group) of infants aged 3 months were surveyed through a self-reported questionnaire from April 2018 to March 2019. The experience of baby-friendly practices and breastfeeding during hospitalization were assessed with yes/no questions. Socio-demographic factors that influenced breastfeeding at 3 months were analyzed using bivariate and multivariate logistic regression analyses. RESULTS: Of mothers in the EBF group, 65.57% reported engaging in at least seven baby-friendly practices compared to 47.72% of mothers in the NBF group. Significantly more mothers in the EBF group engaged in baby-friendly practices than in the NBF group. These practices included "breastfeeding within one hour after birth" (74.29% vs. 59.09%), "breastfeeding on demand" (86.48% vs. 75.00%), and "never use a pacifier" (46.53% vs. 31.25%). After adjusting for confounding variables, we found that the mothers who engaged in fewer than seven baby-friendly practices were about 1.7 times less likely to breastfeed than were those who engaged in seven or more baby-friendly practices (odds ratio [OR] 1.720, 95% confidence interval [CI] 1.106, 2.667). Further, the mothers who did not breastfeed on demand were as likely to not breastfeed up to 3 months (OR 2.263, 95% CI 1.265, 4.049), as were mothers who did not breastfeed during hospitalization (OR 4.379, 95% CI 1.815, 10.563). CONCLUSIONS: These data from hospitals in China suggest that higher compliance with baby-friendly practices may have a positive impact on EBF at 3 months, particularly in terms of promoting the implementation of breastfeeding on demand and breastfeeding during hospitalization in China.

Multiparametric magnetic resonance imaging in the assessment of anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurrent glioblastoma.

EGFRvIII targeted chimeric antigen receptor T (CAR-T) cell therapy has recently been reported for treating glioblastomas (GBMs); however, physiology-based MRI parameters have not been evaluated in this setting. Ten patients underwent multiparametric MRI at baseline, 1, 2 and 3 months after CAR-T therapy. Logistic regression model derived progression probabilities (PP) using imaging parameters were used to assess treatment response. Four lesions from "early surgery" group demonstrated high PP at baseline suggestive of progression, which was confirmed histologically. Out of eight lesions from remaining six patients, three lesions with low PP at baseline remained stable. Two lesions with high PP at baseline were associated with large decreases in PP reflecting treatment response, whereas other two lesions with high PP at baseline continued to demonstrate progression. One patient didn't have baseline data but demonstrated progression on follow-up. Our findings indicate that multiparametric MRI may be helpful in monitoring CAR-T related early therapeutic changes in GBM patients.

Assessment of early response to tumor-treating fields in newly diagnosed glioblastoma using physiologic and metabolic MRI: initial experience.

Tumor-treating fields (TTFields) is a novel antimitotic treatment modality for patients with glioblastoma. To assess response to TTFields, a newly diagnosed patient with glioblastoma underwent diffusion, perfusion and 3D echo-planar spectroscopic imaging prior to initiation of TTFields plus temozolamide (baseline) and at 1- and 2-month follow-up periods. Increased mean diffusivity along with decreased fractional anisotropy and maximum relative cerebral blood volume were noted at 2 months relative to baseline suggesting inhibition of tumor growth and angiogenesis. Additionally, a reduction in choline/creatine was also noted during this period. These preliminary data indicate the potential of physiologic and metabolic MRI in assessing early treatment response to TTFields in combination with temozolamide.

[Exposure risk assessment of plasticizer in dietary food in Xiamen].

OBJECTIVE: To understand the dietary consumption of residents in Xiamen and the content of phthalic acid esters (PAEs) in food, and to assess the plasticizer exposure risk of diet in Xiamen. METHODS: The survey was conducted by stratified cluster random sampling method in Xiamen from September to October in 2010. According to the Xiamen administrative division, six neighborhood communities were selected as sampling units, then 25 families were randomly chosen from each sampling units.From the above 150 families, the permanent residents over the age of six were permitted to our study. The survey included 495 residents totally. These participants' information, such as basic personal information, physical activity levels, meal frequency and the average consumption of 33 kinds of food in 13 categories were collected using questionnaires. Thirteen categories included cereal and tubers, beans, vegetables, fungi and algae, fruits, dairy products, meat, seafood, eggs, snacks, beverages, cooking oil and spices. The height and weight of residents were measured and the average daily dietary intake was calculated. Thirty-three kinds of food in 13 categories were collected in supermarkets in Xiamen. According to the annual sales ranking, the top three-five brands of each kinds of food were selected and numbered, then two or three brands were chosen by random number table method from them; three completely individual packed samples in the same batch of each brand were detected; 243 samples were included in our study.100-500 g solid samples or 100-500 ml liquid samples were collected. The content of diethyl phthalate (DEP), dibutyl phthalate (DBP), di (2-ethylhexyl) phthalate (DEHP) in food were detected by liquid chromatography mass spectrometry, which expressed by median (minimum-maximum). The exposure dose, contribution rate and risk index of PAEs were calculated by point estimation method. RESULTS: According to the average daily dietary intake of residents in Xiamen, the top three ones in 13 categories of food were cereal and tubers (337.16 g/d, 18.21%), vegetables (309.12 g/d, 16.69%) and fruits (213.20 g/d, 11.51%). The content of DEP, DBP or DEHP among different categories of food was significantly different (χ² values were 58.05, 50.19 and 102.10, P < 0.01). Among 13 categories of food, seafood contained the most DEP (0.090 (0.000-0.324)mg/kg); cooking oil had the most DBP (0.700(0.000-2.980) mg/kg) and DEHP (5.115(0.000-24.160) mg/kg). DEP, DBP and DEHP exposure(0.19, 4.20, 18.10 µg × kg⁻¹ ×d ⁻¹)in dietary food in Xiamen were less than the reference dose(RfD) (800, 100, 20 µg × kg⁻¹ × d⁻¹) proposed by the United States Environmental Protection Agency (EPA), and the risk indexes were 0.02%, 4.20% and 90.50%, respectively. Among 13 categories of foods, seafood was the main source of DEP dietary exposure. The exposure dose and contribution rate of DEP in seafood were 0.18 µg × kg⁻¹ × d⁻¹ and 94.74%, respectively.Vegetables were the main source of DBP and DEHP dietary exposure. The exposure dose and contribution rate of DBP and DEHP were 1.48 µg × kg⁻¹ × d⁻¹, 35.24% and 6.07 µg × kg⁻¹ × d⁻¹, 33.54%, respectively. CONCLUSION: The food consumed by residents in Xiamen was overall in a safe state, but to some extent, there still exists DEHP exposure risk in foods.