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INTRODUCTION: Anal cancer (AC) is 18 F-FDG-PET avid and has been used to evaluate treatment response several months after chemoradiotherapy. This pilot study aimed to assess the utility of semi-automated contouring methods and quantitative measures of treatment response using 18 F-FDG-PET imaging at the early time point of 1-month post-chemoradiotherapy. METHODS: Eleven patients with AC referred for chemoradiotherapy were prospectively enrolled into this study, with 10 meeting eligibility requirements. 18 F-FDG-PET imaging was obtained pre-chemoradiotherapy (TP1), and then 1-month (TP2), 3-6 months (TP3) and 9-12 months (TP4) post-chemoradiotherapy. Manual and semi-automated (Threshold) contouring methods were used to define the primary tumour on all 18 F-FDG-PET images. Resultant contours from each method were interrogated using quantitative measures, including volume, response index (RI), total lesion glycolysis (TLG), SUVmax , SUVmedian and SUVmean . Response was assessed quantitatively as reductions in these measures and also qualitatively against established criteria. RESULTS: Nine patients were qualitatively classified as complete metabolic responders at TP2 and all 10 at TP3. All quantitative measures demonstrated significant (P < 0.05) reductions at TP2 for both Manual and Threshold methods. All reduced further at TP3 and again at TP4 for Threshold methods. TLG showed the highest reduction at all post-chemoradiotherapy time points and classified the most responders for each method at each time point. All patients are recurrence-free at minimum 4-year follow-up. CONCLUSION: Based on our small sample size, semi-automated methods of disease definition using 18 F-FDG-PET imaging are feasible and appear to facilitate quantitative response classification of AC as early as 1-month post-chemoradiotherapy. Early identification of treatment response may potentially improve disease management.

Recently, the realization of minimally invasive medical interventions on targeted tissues using wireless small-scale medical robots has received an increasing attention. For effective implementation, such robots should have a strong adhesion capability to biological tissues and at the same time easy controlled detachment should be possible, which has been challenging. To address such issue, a small-scale soft robot with octopus-inspired hydrogel adhesive (OHA) is proposed. Hydrogels of different Young's moduli are adapted to achieve a biocompatible adhesive with strong wet adhesion by preventing the collapse of the octopus-inspired patterns during preloading. Introduction of poly(N-isopropylacrylamide) hydrogel for dome-like protuberance structure inside the sucker wall of polyethylene glycol diacrylate hydrogel provides a strong tissue attachment in underwater and at the same time enables easy detachment by temperature changes due to its temperature-dependent volume change property. It is finally demonstrated that the small-scale soft OHA robot can efficiently implement biomedical functions owing to strong adhesion and controllable detachment on biological tissues while operating inside the body. Such robots with repeatable tissue attachment and detachment possibility pave the way for future wireless soft miniature robots with minimally invasive medical interventions., Max Planck Society; International Max Planck Research School for Intelligent Systems; Alexander von Humboldt Foundation; Projekt DEAL

Objective To examine the efficacy of hyperimmunoglobulin (HIG) treatment in women with a recent primary cytomegalovirus (CMV) infection up to 14weeks' gestation. Methods This is an ongoing observational study conducted at the prenatal medicine departments of the University Hospitals of Tubingen, Bonn, Cologne and Erlangen, Germany, as well as at the Laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tubingen, Tubingen, Germany. Enrolment criteria were the presence of confirmed recent primary CMV infection in the first trimester and a gestational age at first HIG administration of <= 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti-immunoglobulin (Ig)-G levels, low anti-CMV-IgG avidity in the presence of a positive CMV-IgM test and no positive reactivity or just sero-conversion anti-gB2-IgG-reactivity. HIG administration was started as soon as possible within a few days after the first visit. HIG was administered intravenously at a dose of 200 IU/kg maternal body weight and repeated every 2 weeks until about 18 weeks' gestation. The primary outcome was maternal-fetal transmission at the time of amniocentesis. Multivariate logistic regression analysis was used to determine significant covariates that could predict maternal-fetal transmission. Results We included 149 pregnancies (153 fetuses) that completed the treatment. Median maternal age and weight were 32.0 years and 65.0 kg, respectively. Median gestational age at the time of first referral to one of the four centers was 9.4weeks. Median anti-CMV-IgG level, anti-CMV-IgM index and CMV-IgG avidity were 5.7U/mL, 2.5 and 22.3%, respectively. HIG treatment was started at a median gestational age of 10.6weeks and ended at a median of 17.9weeks. Within this time frame, HIG was administered on average four times in each patient. Amniocentesis was carried out at a median gestational age of 20.4weeks. In 14

INTRODUCTION: Guidelines recommend that the proximal seminal vesicles (PrSV) should be included in the clinical target volume for locally advanced prostate cancer patients undergoing radiotherapy. Verification and margins for the prostate may not necessarily account for PrSV displacement. The purpose was to determine the inter-fraction displacement of the PrSV relative to the prostate during radiotherapy. METHODS: Fiducials were inserted into the prostate, and right and left PrSV (RSV and LSV) in 30 prostate cancer patients. Correctional shifts for the prostate, right and left PrSV and pelvic bones were determined from each patient's 39 daily orthogonal portal images relative to reference digitally reconstructed radiographs. RESULTS: There was a significant displacement of the RSV relative to the prostate in all directions: on average 0.38 mm (95% confidence interval (CI) 0.26 to 0.50) to the left, 0.80-0.81 mm (CI 0.68 to 0.93) superiorly and 1.51 mm (CI 1.36 to 1.65) posteriorly. The LSV was significantly displaced superiorly to the prostate 1.09-1.13 mm (CI 0.97 to 1.25) and posteriorly 1.81 mm (CI 1.67 to 1.96), but not laterally (mean 0.06, CI -0.06 to 0.18). The calculated PTV margins (left-right, superior-inferior, posterior-anterior) were 4.9, 5.3-5.6 and 4.8 mm for the prostate, 5.2, 7.1-8.0 and 9.7 mm for the RSV, and 7.2, 7.5-7.6 and 8.6 mm for the LSV. CONCLUSION: There is a significant displacement of the PrSV relative to the prostate during radiotherapy. Greater margins are recommended for the PrSV compared to the prostate.

Controlled microrobotic navigation in the vascular system can revolutionize minimally invasive medical applications, such as targeted drug and gene delivery. Magnetically controlled surface microrollers have emerged as a promising microrobotic platform for controlled navigation in the circulatory system. Locomotion of micrororollers in strong flow velocities is a highly challenging task, which requires magnetic materials having strong magnetic actuation properties while being biocompatible. The L10-FePt magnetic coating can achieve such requirements. Therefore, such coating has been integrated into 8 µm-diameter surface microrollers and investigated the medical potential of the system from magnetic locomotion performance, biocompatibility, and medical imaging perspectives. The FePt coating significantly advanced the magnetic performance and biocompatibility of the microrollers compared to a previously used magnetic material, nickel. The FePt coating also allowed multimodal imaging of microrollers in magnetic resonance and photoacoustic imaging in ex vivo settings without additional contrast agents. Finally, FePt-coated microrollers showed upstream locomotion ability against 4.5 cm s?1 average flow velocity with real-time photoacoustic imaging, demonstrating the navigation control potential of microrollers in the circulatory system for future in vivo applications. Overall, L10-FePt is conceived as the key material for image-guided propulsion in the vascular system to perform future targeted medical interventions., Max Planck Institute; Projekt DEAL

INTRODUCTION: Precision radiotherapy relies heavily on optimal weight management. Our group previously developed a risk stratification model for patients at risk of prolonged feeding tube (FT) intervention. The study objective was to assess on-treatment weight loss according to stratified risk of prolonged FT use. METHODS: One hundred and one (n = 101) definitive head and neck radiotherapy patients were included in this study. Patients were stratified into high risk (HRi: T-classification ≥ 3 with level 2 Nodal disease), high-intermediate risk (HIRi: T-classification ≥ 3 without level 2 Nodes) and low-intermediate risk (LIRi: T-classification < 3 with level 2 Nodes) of prolonged FT use. Demographic variables and on-treatment weight loss were evaluated according to risk status. RESULTS: Oropharyngeal carcinoma (OPC) was present in a larger proportion in the LIRi cohort (HRi: 71%, HIRi: 52%, LIRi: 81%, P = 0.008). LIRi patients were more likely to have human papilloma virus (HPV)-associated disease (88%, P = 0.001). Never/minimal smoking (P = 0.003), good performance status (P < 0.001), healthy BMI (P = 0.050) and no pre-existing dysphagia (P < 0.001) were predominant within the LIRi prognostic group. LIRi patients lost significantly more weight in total (HRi = 4.8% vs. LIRi = 8.2%, P = 0.002; HIRi = 5.2% vs. LIRi = 8.2%, P = 0.006) and when using a FT (HRi = 4.6% vs. LIRi = 8.8%, P < 0.001; HIRi = 5.3% vs. LIRi = 8.8%, P = 0.002). CONCLUSIONS: Patients identified as low-intermediate risk of prolonged, ≥25% FT use report significantly increased weight loss compared with patients at higher risk of FT use. This cohort is typical of the increasing number of patients presenting with HPV-associated OPC. Results of this study suggest we should closely observe such patients throughout treatment, to ensure optimal weight maintenance, facilitating precision radiotherapy.

BACKGROUND: The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. METHODS: One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. RESULTS: Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. CONCLUSION: In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use.

INTRODUCTION: Our department commonly uses a planning target volume (PTV) expansion of 6 mm posterior and 1 cm in all other directions when treating prostate cancer patients with image-guided radiotherapy (IGRT). This study aimed to test the adequacy of this PTV expansion by assessing geographical miss of the prostate on post-treatment cone-beam CT (CBCT) and identify those at risk of geographical miss. METHODS: Twenty-two prostate cancer patients receiving IGRT with implanted fiducial markers underwent daily pre-treatment orthogonal kV imaging followed by a post-treatment CBCT for a total of 432 fractions. The prostate was outlined on all CBCTs. For each imaging set, the volume of geographic miss was measured by subtracting the PTV from the planning CT and prostate volume on the post-treatment CBCT. RESULTS: The prostate volume moved outside the PTV by >0.01 cc in 9% of fractions (39/432). This occurred in 13 (59%) of 22 patients. Large prostates >40 cc and >50 cc had significantly more geographical miss events (both P < 0.001). Changes in rectal filling appear to be responsible for prostate motion/deformation in 82% (32/39) of fractions. CONCLUSIONS: Our analysis suggests that, despite IGRT, prostate PTV margins are not adequate in some patients, particularly those with large prostates. PTV margins may be reduced in some other patients. Prostate rotation and deformation play an important role in setting margins and may not always be represented accurately by fiducial marker displacements. Individualised and adaptive margins for prostate cancer patients should be a priority for future research.