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[en] Hydrophobicity is known to play a key role in the biological distribution of materials but is often an overlooked parameter when conjugating targeting agents, drugs, and dyes to dendrimers. This review examines the impact of hydrophobic variation in stochastically conjugated dendrimers as well as materials where synthetic methods or approaches to purification provide more controlled samples. Hydrophobic interactions are considered for three general classes: (1) terminal functional group modifications, (2) bioactive small molecules chosen to interact with receptors and proteins as targeting agents and/or drugs, and (3) imaging agents to track biological activity. Impacts on membrane interaction and cellular uptake, biodistribution, interaction with transport proteins, and pharmacokinetics are discussed. The size range of the dendrimers discussed is ~ 1–10 nm.
[en] The limited positive predictive value of an incomplete response on PET-CT following (chemo)radiotherapy for head and neck squamous cell carcinoma (HNSCC) means that the optimal management strategy remains uncertain. The aim of the study is to assess the utility of a ‘second-look’ interval PET-CT. Patients with HNSCC who were treated with (chemo)radiotherapy between 2008 and 2017 and underwent (i) baseline and (ii) response assessment PET-CT and (iii) second-look PET-CT following incomplete (positive or equivocal scan) response were included. Endpoints were conversion rate to complete response (CR) and test characteristics of the second-look PET-CT. Five hundred sixty-two patients with HNSCC underwent response assessment PET-CT at a median of 17 weeks post-radiotherapy. Following an incomplete response on PET-CT, 40 patients underwent a second-look PET-CT at a median of 13 weeks (range 6–25) from the first response PET-CT. Thirty-four out of 40 (85%) patients had oropharyngeal carcinoma. Twenty-four out of 40 (60%) second-look PET-CT scans converted to a complete locoregional response. The primary tumour conversion rate was 15/27 (56%) and the lymph node conversion rate was 14/19 (74%). The sensitivity, specificity, positive predictive value and negative predictive value (NPV) of the second-look PET-CT were 75%, 75%, 25% and 96% for the primary tumour and 100%, 92%, 40% and 100% for lymph nodes. There were no cases of progression following conversion to CR in the primary site or lymph nodes. The majority of patients who undergo a second-look PET-CT convert to a CR. The NPV of a second-look PET-CT is high, suggesting the potential to avoid surgical intervention.
[en] To explore the utility of MR texture analysis (MRTA) for detection of nodal extracapsular spread (ECS) in oral cavity squamous cell carcinoma (SCC). 115 patients with oral cavity SCC treated with surgery and adjuvant (chemo)radiotherapy were identified retrospectively. First-order texture parameters (entropy, skewness and kurtosis) were extracted from tumour and nodal regions of interest (ROIs) using proprietary software (TexRAD). Nodal MR features associated with ECS (flare sign, irregular capsular contour; local infiltration; nodal necrosis) were reviewed and agreed in consensus by two experienced radiologists. Diagnostic performance characteristics of MR features of ECS were compared with primary tumour and nodal MRTA prediction using histology as the gold standard. Receiver operating characteristic (ROC) and regression analyses were also performed. Nodal entropy derived from contrast-enhanced T1-weighted images was significant in predicting ECS (p = 0.018). MR features had varying accuracy: flare sign (70%); irregular contour (71%); local infiltration (66%); and nodal necrosis (64%). Nodal entropy combined with irregular contour was the best predictor of ECS (p = 0.004, accuracy 79%). First-order nodal MRTA combined with imaging features may improve ECS prediction in oral cavity SCC. (orig.)
[en] To evaluate the utility of a standardized qualitative scoring system for treatment response assessment at 18F-FDG PET-CT in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma and correlate this with subsequent patient outcome. Ninety-six consecutive patients with locally advanced cervical carcinoma treated with radical chemoradiotherapy (CRT) in a single centre between 2011 and 2014 underwent 18F-FDG PET-CT approximately 3 months post-treatment. Tumour metabolic response was assessed qualitatively using a 5-point scale ranging from background level activity only through to progressive metabolic disease. Clinical and radiological (MRI pelvis) follow-up was performed in all patients. Progression-free (PFS) and overall survival (OS) was calculated using the Kaplan-Meier method (Mantel-Cox log-rank) and correlated with qualitative score using Chi-squared test. Forty patients (41.7 %) demonstrated complete metabolic response (CMR) on post-treatment PET-CT (Score 1/2) with 38 patients (95.0 %) remaining disease free after a minimum follow-up period of 18 months. Twenty-four patients (25.0 %) had indeterminate residual uptake (ID, Score 3) at primary or nodal sites after treatment, of these eight patients (33.3 %) relapsed on follow-up, including all patients with residual nodal uptake (n = 4). 11 of 17 patients (64.7 %) with significant residual uptake (partial metabolic response, PMR, Score 4) subsequently relapsed. In 15 patients (15.6 %) PET-CT demonstrated progressive disease (PD, Score 5) following treatment. Kaplan-Meier analysis showed a highly statistically significant difference in PFS and OS between patients with CMR, indeterminate uptake, PMR and PD (Log-rank, P < 0.0001). Chi-squared test demonstrated a highly statistically significant association between increasing qualitative score and risk of recurrence or death (P < 0.001). Use of a 5-point qualitative scoring system to assess metabolic response to CRT in locally advanced cervical carcinoma predicts survival outcome and this prognostic information may help guide further patient management. (orig.)