Magnetic Resonance Imaging (MRI) is an important diagnostic scanning tool for the detection and monitoring of specific diseases and conditions. However, the equipment cost, maintenance and specialty training of the technologists make the examination expensive. Consequently, unnecessary scanner time caused by poor scheduling, repeated sequences, aborted sequences, scanner idleness, or capture of non-diagnostic or low-value sequences is an opportunity to reduce costs and increase efficiency. This paper analyzes data collected from log files on 29 scanners over several years. 'Wasted' time is defined and key performance indicators (KPIs) are identified. A decrease in exam duration results when actively modifying and monitoring the number of sequences that comprise the exam card for a protocol.

PDF file 92K, Figure S4 shows the effect of metformin on bRFR in the matched cohort of 172 prostate cancer patients

Liposome-based anticancer agents take advantage of the increased vascular permeability and transvascular pressure gradients for selective accumulation in tumors, a phenomenon known as the enhanced permeability and retention(EPR) effect. The EPR effect has motivated the clinical use of nano-therapeutics, with mixed results on treatment outcome. High interstitial fluid pressure (IFP) has been shown to limit liposome drug delivery to central tumour regions. Furthermore, high IFP is an independent prognostic biomarker for treatment efficacy in radiation therapy and chemotherapy for some solid cancers. Therefore, accurately measuring spatial liposome accumulation and IFP distribution within a solid tumour is crucial for optimal treatment planning. In this paper, we develop a model capable of predicting voxel-by-voxel intratumoral liposome accumulation and IFP using pre and post administration imaging. Our approach is based on physics informed machine learning, a novel technique combining machine learning and partial differential equations. through application to a set of mouse data and a set of synthetically-generated tumours, we show that our approach accurately predicts the spatial liposome accumulation and IFP for an individual tumour while relying on minimal information. This is an important result with applications for forecasting tumour progression and designing treatment.

PDF file 81K, Supplementary Legends

PDF file 209K, Figure S1 illustrates the method for IHC analysis. It also shows a reduction in hypoxic fraction after metformin exposure in POP-92S and LNCaP xenografts

PDF file 80K, Figure S2 shows data from in vitro and ex vivo clonogenic assays of metformin treatment in combination with radiation

PDF file 54K, Figure S5 shows blood glucose levels in mice after metformin treatment

PDF file 77K, Figure S3 shows propensity score distribution in the unmatched and matched patient cohort

PDF file 97K, Table S1 shows the clinical demographics of the patient cohort treated with radiotherapy for prostate cancer

BACKGROUND:COVID-19 was declared a pandemic by the World Health Organization on March 11th, 2020. Global social lockdowns were instigated to reduce spread and prevent health-services from becoming overwhelmed. People having treatment for cancer are known to have heightened psychological/emotional burden. The combined impact of managing pandemic regulations alongside this may present additional burden. The purpose of this systematic review is to examine current evidence of the psychological and emotional impact of COVID-19 on people with cancer, early in the pandemic. METHODS:Five electronic databases were searched (Embase, Global Health, HMIC, PsychINFO, CINAHL) from September 2019 to October 2021. Qualitative, quantitative and mixed-method primary research studies exploring emotional and psychological impacts of COVID-19 on cancer patients, limited to English language, were included. Quality appraisal was conducted using the MMAT. RESULTS:Fifty-one papers, with 27,356 people from 21 countries treated for cancer, were included. 43 studies were quantitative with a survey method approach, six studies qualitative and four used a mixed methods design. MMAT score was mostly two or three. Four themes were identified: Emotional aspects and Quality of Life; Psychosocial aspects; Impact of COVID-19 on self; Impact of COVID-19 on cancer, with themes overlapping. CONCLUSION:Whilst emotional/psychological impacts such as anxiety, isolation, employment fears, and uncertainty about the future were potentially universal concerns early in the pandemic, they may have been particularly acute for people living with cancer and represent complex, overlapping factors. As COVID-19 continues to impact health-services and society, it is important to focus on any ongoing impact to the experience of cancer patients. Most of the studies reviewed used tools that do not provide deeper understanding of how and why emotional states of people with cancer were affected. Further qualitative work may reveal patterns of what was unique to cancer patients during the pandemic, compared to general populations.

Background: Virtualization in radiology presents a growing opportunity to improve the efficiency and lower the cost of care delivery. Furthermore, it may provide a means to manage staffing shortages, reduce burnout, and encourage employee development. In radiology, the feasibility to perform several non-patientfacing imaging procedure tasks remotely is explored. Virtualization of magnetic resonance imaging (MRI) exams is of specific interest as it typically involves a range of complex tasks, and inefficiencies can increase patient wait times (WTs) and reduce overall utilization. Methods: To explore this, a computer simulation model is developed to approximate turn-around time (TAT) and patient WT while accounting for technologist expertise and workflow complexity. The model was validated against 1,618 magnetic resonance (MR) inpatient/ED exams. Using cognitive task analysis (CTA), complex MR functions are identified from a technologist perspective that may require a high-level of expertise and thus influence workflow durations. Results: Virtualizing complex, non-patient-facing functions may reduce MR workflow duration by up to 15% and patient in-exam WT by up to 75% when utilizing expert technologists. For example, scans involving the abdomen and spine and addressing unreported implants benefit the most from experts and may be supported remotely. Conclusions: Modifying the workflow of MRI exams by segmenting complex, non-patient facing functions to expert technologists within an organization or in a remote center is feasible as it improves efficiencies and results in a better patient experience. In addition, administration now has guidance on how to effectively deploy a highly-trained workforce in a virtual setting.

The decision to participate in phase I cancer clinical trials can be complex. Prior studies have suggested that some patients on early phase trials may not fully appreciate the purpose, risks and low chance of benefit. Question Prompt Lists (QPL) have proven benefit in studies across different medical specialties in empowering the patient to participate in their consultation. Although there is literature assessing the value of QPLs in cancer clinical trials, it has not been explored specifically in the phase I setting.

IC for Ph I trials is difficult as pts can misunderstand key design aspects; recent Ph I trial successes (eg. immune checkpoint inhibition) have further complicated the situation. We aimed to measure the quality of IC in our centre using a validated instrument testing objective (obj) and subjective (sub) understanding of key IC domains including trial purpose, risks and benefits. We identified consecutive patients on Ph I trials in our unit from Sep - Dec 2019, collected demographic data, and administered Quality of Informed Consent Part A (QuIC-A,20 items, obj) and Part B (QuIC-B,14 items, sub). Primary endpoints were summary scores on QuIC-A and QuIC-B. No pts declined. All pts had undergone standard IC processes including access to extensive written material and at least 2 clinic appointments prior to consent. 36 pts were evaluable - 19 (53%) were in a Ph I dose escalation trial and 17 (47%) were in a Ph I dose expansion trial. 18 (50%) were female, 16 (44%) were over the age of 65, 21 (58%) had a university education and 35 (97%) spoke English as their first language. 21 (58%) had been on trial for less than two months. The average QuIC-A (obj) score was 76 out of 100 (SD 10, 58–97) while QuIC -B (sub) score was 91 out of 100 (SD 8, 68–100). 100% (n=36) correctly identified that they were in a clinical trial and 81% (n=29) that they would be able to withdraw at any point. However, 15 (41%) reported that all treatments in their trial were standard for their type of cancer while 10 (28%) reported that their trial did not carry any additional risks or discomforts compared to standard treatments. 23 (61%) pts reported that they had not been offered alternatives to trial participation. There was no correlation between sub and obj scores (R2 = 0.005). In planned analyses (two sample t-test), university education had a numerical benefit on obj score (76 vs 71, p=0.29) while age over 65 had no impact (76 vs 75, p=0.91). While pts in our Ph I trials unit showed an excellent grasp of some aspects of clinical trials, they showed deficits in key domains of IC for clinical trials. This study demonstrates the need for research into interventions which can improve IC for Ph I pts.

Motion artifacts are a common occurrence in Magnetic Resonance Imaging exam. Motion during acquisition has a profound impact on workflow efficiency, often requiring a repeat of sequences. Furthermore, motion artifacts may escape notice by technologists, only to be revealed at the time of reading by the radiologists, affecting their diagnostic quality. There is a paucity of clinical tools to identify and quantitatively assess the severity of motion artifacts in MRI. An image with subtle motion may still have diagnostic value, while severe motion may be uninterpretable by radiologists and requires the exam to be repeated. Therefore, a tool for the automatic identification of motion artifacts would aid in maintaining diagnostic quality, while potentially driving workflow efficiencies. Here we aim to quantify the severity of motion artifacts from MRI images using deep learning. Impact of subject movement parameters like displacement and rotation on image quality is also studied. A state-of-the-art, stacked ensemble model was developed to classify motion artifacts into five levels (no motion, slight, mild, moderate and severe) in brain scans. The stacked ensemble model is able to robustly predict rigid-body motion severity across different acquisition parameters, including T1-weighted and T2-weighted slices acquired in different anatomical planes. The ensemble model with XGBoost metalearner achieves 91.6% accuracy, 94.8% area under the curve, 90% Cohen's Kappa, and is observed to be more accurate and robust than the individual base learners.

Study Objective To present a unique case of the workup and management of recurrent colorectal endometriosis utilizing a multidisciplinary team approach. Design Case Report. Setting Community teaching hospital. Collaborative robotic surgical team including a minimally invasive gynecologic surgeon and colorectal surgeon utilizing the Da Vinci Xi platform. Patients or Participants 38-year-old gravida 3, para 1 with a history of deeply-infiltrating endometriosis status post excisional surgery including shave excision of a colorectal implant six months prior. She presents with recurrent rectal pain and bleeding due to confirmed recurrent colorectal endometriosis. Interventions Following a multi-disciplinary case conference, colorectal surgery performed a robotic-assisted low anterior bowel resection with primary colorectal anastomosis and flexible sigmoidoscopy. Gynecology was present to confirm all endometriosis excised and fertility was optimized for future planned frozen embryo transfer. Measurements and Main Results Complete excision of colorectal endometriosis with resolution of patient's rectal pain and bleeding. Pathology showed transmural colorectal endometriosis including a rectal lymph node involved with endometriosis. Conclusion Unusual case of recurrent colorectal endometriosis following shave excision, managed with segmental colorectal resection. Endometriosis involving a lymph node shows the disease's ability to be locally invasive however this phenomenon is not thought to lead to higher recurrence rates. To present a unique case of the workup and management of recurrent colorectal endometriosis utilizing a multidisciplinary team approach. Case Report. Community teaching hospital. Collaborative robotic surgical team including a minimally invasive gynecologic surgeon and colorectal surgeon utilizing the Da Vinci Xi platform. 38-year-old gravida 3, para 1 with a history of deeply-infiltrating endometriosis status post excisional surgery including shave excision of a colorectal implant six months prior. She presents with recurrent rectal pain and bleeding due to confirmed recurrent colorectal endometriosis. Following a multi-disciplinary case conference, colorectal surgery performed a robotic-assisted low anterior bowel resection with primary colorectal anastomosis and flexible sigmoidoscopy. Gynecology was present to confirm all endometriosis excised and fertility was optimized for future planned frozen embryo transfer. Complete excision of colorectal endometriosis with resolution of patient's rectal pain and bleeding. Pathology showed transmural colorectal endometriosis including a rectal lymph node involved with endometriosis. Unusual case of recurrent colorectal endometriosis following shave excision, managed with segmental colorectal resection. Endometriosis involving a lymph node shows the disease's ability to be locally invasive however this phenomenon is not thought to lead to higher recurrence rates.

Background Extensive research has demonstrated that patients considering early phase oncology trials do not appreciate the design or purpose of these trials and also harbour unrealistic expectations of the personal benefit they can expect from the trial. There have been few interventional studies examining the informed consent process in this setting and they have shown limited effectiveness. We aimed to use a qualitative methodology to understand the perspectives of key stakeholders and identify the areas of need and the potential opportunities for an intervention to improve our informed consent processes. Methods We used an experience-based co-design framework which consisted of a semi-structured interview script of ten key questions. Two trained interviewers performed interviews of three consultant medical oncologists, nine clinical fellows, two study managers, two clinical nurse specialists, two focus groups with four patients each and two regulatory officers. We also interviewed four members of our investigator-initiated sponsor team to obtain an understanding of the sponsor perspective. All audio interviews were transcribed, and thematic analysis was performed on the narrative text to extract core themes. Results Consistent themes raised by participants included 1. The core elements that participants need to comprehend prior to consenting are that trials are experiments and not treatment, the low prospect of benefit, potential toxicity and the significant time commitment. 2. Participant information sheets (PIS) are too long, too complex and the information is not provided in a patient centred manner. Sponsors were in strong support of shorter and more accessible PIS. 3. Digital media would be acceptable and useful but to be mindful of subgroups of patients who are not as comfortable with digital media. Conclusions There is widespread understanding that improvement is required in the length, design and style of participant information sheets for phase 1 oncology trials. Furthermore, digital media would be acceptable to all stakeholders but its development will require ongoing stakeholder engagement to ensure user acceptability. Legal entity responsible for the study Drug Development Unit - Royal Marsden Hospital, Sutton. Funding Cancer Research UK (CRUK), Experimental Cancer Medicine Centres (ECMC), National Institute of Health Research (NIHR) Royal Marsden Biomedical Research Centre. Disclosure J. Lopez: Advisory / Consultancy: Genmab; Advisory / Consultancy: Novartis; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Basilea; Travel / Accommodation / Expenses: Basilea; Travel / Accommodation / Expenses: Roche/Genentech. All other authors have declared no conflicts of interest.

Nanomedicine drug delivery systems are capable of transporting significant payloads to solid tumors. However, only a modest increase in antitumor efficacy relative to the standard of care has been observed. In this study, we demonstrate that a single dose of radiation or mild hyperthermia can substantially improve tumor uptake and distribution of nanotherapeutics, resulting in improved treatment efficacy. The delivery of nanomedicine was driven by a reduction in interstitial fluid pressure (IFP) and small perturbation of steady-state fluid flow. The transient effects on fluid dynamics in tumors with high IFP was also shown to dominate over immune cell endocytic capacity, another mechanism suspected of improving drug delivery. Furthermore, we demonstrate the specificity of this mechanism by showing that delivery of nanotherapeutics to low IFP tumors with high leukocyte infiltration does not benefit from pretreatment with radiation or heat. These results demonstrate that focusing on small perturbations to steady-state fluid dynamics, rather than large sustained effects or uncertain immune cell recruitment strategies, can impart a vulnerability to tumors with high IFP and enhance nanotherapeutic drug delivery and treatment efficacy.

The flexibility and sophistication of modern radiotherapy treatment planning and delivery methods have advanced techniques to improve the therapeutic ratio. Contemporary dose optimization and calculation algorithms facilitate radiotherapy plans which closely conform the three-dimensional dose distribution to the target, with beam shaping devices and image guided field targeting ensuring the fidelity and accuracy of treatment delivery. Ultimately, dose distribution conformity is limited by the maximum deliverable dose gradient; shallow dose gradients challenge techniques to deliver a tumoricidal radiation dose while minimizing dose to surrounding tissue. In this work, this ‘dose delivery resolution’ observation is rigorously formalized for a general dose delivery model based on the superposition of dose kernel primitives. It is proven that the spatial resolution of a delivered dose is bounded by the spatial frequency content of the underlying dose kernel, which in turn defines a lower bound in the minimization of a dose optimization objective function. In addition, it is shown that this optimization is penalized by a dose deposition strategy which enforces a constant relative phase (or constant spacing) between individual radiation beams. These results are further refined to provide a direct, analytic method to estimate the dose distribution arising from the minimization of such an optimization function. The efficacy of the overall framework is demonstrated on an image guided small animal microirradiator for a set of two-dimensional hypoxia guided dose prescriptions.

Background: Advances in the understanding of the biological basis of cancer have resulted in a paradigm shift in drug development. Phase I trials with translational elements are conducted in clinical trials units for patients with cancer. The objective of this study was to evaluate any unmet needs of support and information for patients on Phase I trials. The aim was to utilise patient exerience to assess the need to change or develop delivery of information and support. Methods: A qualitative approach was used. Patients and relatives of patients with cancer on Phase I trials formed two focus group. Group 1 consisted of 8 participants and group 2 10 participants, both lasted one hour. A semi structured schedule was used to prompt discussion, the focus groups were audio-recorded and transcribed verbatim. The data were organised using the Nvivo software package and analysed using Braun and Clarke's thematic analysis framework. Results: Four themes emerged from the data 1) face to face support; there was a general consensus that the best way to recieve information about treatment and disease was face to face. The relationships with the clinical staff were strong and important to maintain. At times when the trials unit was not accessible patients felt vulnerable 2) remote support; email was felt to be a good way to communicate information regarding appointments, the telephone clinic was useful for contact regarding sympton issues. Digital methods of information and support were potentially useful but needed to be thought through properly 3) getting the right information, at the right time , in the right way; patients felt that they needed extra information particularly in terms of feedback regarding the trials and signposting to support services 4) Relationships with other patients; this theme was about the benefit and value patients had in supporting each other within the treatment areas, however this was conflicted and may require extra support at times as there was a negative impact when fellow patients became unwell or died. Conclusions: Based on the results from the analysis written patient information was redesigned. A quarterly forum is in development where patients can meet recieve well being advice and also feedback regarding the trials they are participating in. Legal entity responsible for the study: Royal Marsden NHS Foundation Trust. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.