tbuckley/cabot-search huggingface dataset:
OS08.6.A Glioblastoma treatment response machine learning monitoring biomarkers: a systematic review and meta-analysis
Authors: T C Booth, A Chelliah, A Roman, A Al Busaidi, H Shuaib, A Luis, A Mirchandani, B Alparslan, N Mansoor, K Ashkan, S Ourselin, M Modat, M Grzeda
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The aim of the systematic review was to assess recently published studies on diagnostic test accuracy of glioblastoma treatment response monitoring biomarkers in adults, developed through machine learning (ML). MATERIAL AND METHODS PRISMA methodology was followed. Articles published 09/2018-01/2021 (since previous reviews) were searched for using MEDLINE, EMBASE, and the Cochrane Register by two reviewers independently. Included study participants were adult patients with high grade glioma who had undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide) and subsequently underwent follow-up imaging to determine treatment response status (specifically, distinguishing progression/recurrence from progression/recurrence mimics - the target condition). Risk of bias and applicability was assessed with QUADAS 2. A third reviewer arbitrated any discrepancy. Contingency tables were created for hold-out test sets and recall, specificity, precision, F1-score, balanced accuracy calculated. A meta-analysis was performed using a bivariate model for recall, false positive rate and area-under the receiver operator characteristic curve (AUC). RESULTS Eighteen studies were included with 1335 patients in training sets and 384 in test sets. To determine whether there was progression or a mimic, the reference standard combination of follow-up imaging and histopathology at re-operation was applied in 67% (13/18) of studies. The small numbers of patient included in studies, the high risk of bias and concerns of applicability in the study designs (particularly in relation to the reference standard and patient selection due to confounding), and the low level of evidence, suggest that limited conclusions can be drawn from the data. Ten studies (10/18, 56%) had internal or external hold-out test set data that could be included in a meta-analysis of monitoring biomarker studies. The pooled sensitivity was 0.77 (0.65–0.86). The pooled false positive rate (1-specificity) was 0.35 (0.25–0.47). The summary point estimate for the AUC was 0.77. CONCLUSION There is likely good diagnostic performance of machine learning models that use MRI features to distinguish between progression and mimics. The diagnostic performance of ML using implicit features did not appear to be superior to ML using explicit features. There are a range of ML-based solutions poised to become treatment response monitoring biomarkers for glioblastoma. To achieve this, the development and validation of ML models require large, well-annotated datasets where the potential for confounding in the study design has been carefully considered. Therefore, multidisciplinary efforts and multicentre collaborations are necessary.
OS10.6.A Supportive care needs of TYA childhood brain tumour survivors and their caregivers: a mixed methods study
Authors: E Nicklin, G Velikova, A Glaser, N Sarwar, M Kwok-Williams, M Debono, F Boele
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Childhood brain tumour survivors and their family caregivers can experience many late effects of treatment including social, cognitive and physical issues. Yet, the supportive care needs of survivors, now teenagers and young adults (TYAs), and their caregivers population are largely unknown. We aimed to gain an in-depth understanding of this populations’ supportive care needs. MATERIAL AND METHODS This study used a convergent mixed methods design including quantitative (survey) and qualitative data (in-depth semi-structured interviews). Participants were recruited from long-term follow-up clinics (in three NHS Trusts in England) and online. Participants included childhood brain tumour survivors, at least five years from diagnosis, currently aged 13–30 and their primary caregivers. The results from quantitative and qualitative data were integrated using a Joint Display Table. RESULTS 136 eligible survivors and caregivers (78 survivors/58 caregivers) were approached to take part in the survey. In total, 112 participants (69 survivors/43 caregivers) completed the survey. A further 22 participants took part in face-to-face semi-structured interviews (11 survivors/11 caregivers). The integrated findings indicate that both survivors and caregivers have unmet needs many years after diagnosis. TYA survivors specifically had high unmet needs in relation to their psychological health, social lives (including romantic relationships), employment, and independence. Caregivers experienced even more unmet needs - including regarding their own psychological well-being and survivors’ financial issues. Survivors further from diagnosis, unemployed survivors and single caregivers were more likely to report unmet needs. Barriers preventing survivors and caregivers accessing supportive services were highlighted, including (but not exclusive to) families not being aware of support available, location of services, and accessibility to information/support. CONCLUSION This research provides leads to improving supportive care and long-term follow-up services. Understanding unmet needs and recognising what services are required is critical to improving survivor and caregiver quality of long-term survival.
Causation Research on Diabetic Foot Complications—What I Learned From Roger Pecoraro: The 2021 Roger E. Pecoraro Award Lecture
Authors: Edward J. Boyko
Journal: Diabetes Care (2021)

Roger Pecoraro made important contributions to diabetic foot research and is primarily responsible for instilling in me an interest in these complications. Our collaboration in the final years of his life led to the development of the Seattle Diabetic Foot Study. At the time it began, the Seattle Diabetic Foot Study was perhaps unique in being a prospective study of diabetic foot ulcer conducted in a nonspecialty primary care population of patients with diabetes and without foot ulcer. Important findings from this research include the demonstration that neurovascular measurements, diabetes characteristics, past history of ulcer or amputation, body weight, and poor vision all significantly and independently predict foot ulcer risk. A prediction model from this research that included only readily available clinical information showed excellent ability to discriminate between patients who did and did not develop ulcer during follow-up (area under the receiver operating characteristic curve [AUROC] 0.81 at 1 year). Identification of limb-specific amputation risk factors showed considerable overlap with those risk factors identified for foot ulcer but suggested arterial perfusion as playing a more important role. Risk of foot ulcer in relation to peak plantar pressure estimated at the site of the pressure measurement showed a significant association over the metatarsal heads, but not other foot locations, suggesting that the association between pressure and this outcome may differ by foot location. The Seattle Diabetic Foot Study has helped to expand our knowledge base on risk factors and potential causes of foot complications. Translating this information into preventive interventions remains a continuing challenge.
Sphingosine-1-phosphate transporter spinster homolog 2 is essential for iron-regulated metastasis of hepatocellular carcinoma
Authors: Min Li, Yuxiao Tang, Dongyao Wang, Xiaofeng Zhai, Hui Shen, Chen Zhong, Man Yao, Aiguo Jin, Zhengjun Zhou, Shaolai Zhou, Jia Fan, Chang-quan Ling, Chen Ling
Journal: Molecular Therapy (2021)

Iron dyshomeostasis is associated with hepatocellular carcinoma (HCC) development. However, the role of iron in HCC metastasis is unknown. This study aimed to elucidate the underlying mechanisms of iron's enhancement activity on HCC metastasis. In addition to the HCC cell lines and clinical samples in vitro, iron-deficient (ID) mouse models were generated using iron-free diet and transferrin receptor protein knockout, followed by administration of HCC tumors through either orthotopic or ectopic route. Clinical metastatic HCC samples showed significant ID status, accompanied by overexpression of sphingosine-1-phosphate transporter spinster homolog 2 (SPNS2). Mechanistically, ID increased SPNS2 expression, leading to HCC metastasis in both cell cultures and mouse models. ID not only altered the anti-tumor immunity, which was indicated by phenotypes of lymphatic subsets in the liver and lung of tumor-bearing mice, but also promoted HCC metastasis in a cancer cell autonomous manner through the SPNS2. Since germline knockout of globe SPNS2 showed significantly reduced HCC metastasis, we further developed hepatic-targeting recombinant adeno-associated virus vectors to knockdown SPNS2 expression and to inhibit iron-regulated HCC metastasis. Our observation indicates the role of iron in HCC pulmonary metastasis and suggests SPNS2 as a potential therapeutic target for the prevention of HCC pulmonary metastasis.
Applying treatment advances in castration-resistant prostate cancer: The influence of serial digital education on the uro-oncology team.
Authors: Tariqa Ackbarali, Wendy Turell, Elizabeth L. del Nido, Neal D. Shore
Journal: Journal of Clinical Oncology (2021)

20 Background: Improvements in the understanding of prostate tumor development have spurred advances in biomarker testing and new therapies for prostate cancer, providing clinicians with expanded testing and treatment options. However, these changes have led to competence gaps regarding the use of biomarker testing, integration of PARP inhibitors, application of new data for nmCRPC and mCRPC, and adverse event management. To address these needs, a serial educational initiative was designed for the urology-oncology team. Methods: A 4-part CE activity was launched live-online in December, 2020, and remains on-demand through December, 2021 at UroCareLive.com and OMedLive.com. The activity was launched in partnership with Large Urology Group Practice Association (LUGPA) and included case presentations, live polling, and Q&amp;A. Knowledge and competence questions were administered pre-activity, immediate post-activity, and 2-months post-activity. Patient and clinical practice-impact questions were also asked at the 2-month follow-up. Data from these questions were analyzed to determine engagement and clinical impact. Results: To date, 761 clinicians have participated in the activity. All 12 CE test questions reflected improvements in knowledge and competence, 11 of which were statistically significant. Questions focused on: genomic testing, biomarker analysis, recent clinical trial study results, newly approved therapies, and adverse event management. At 2-mos. follow-up, 70% reported improved behavioral impact on clinical practice and 63% reported impact on patient experience and outcomes. Clinicians provided write-in examples of these changes, illustrating improvements in patient-reported satisfaction, genetic testing, and use of newer therapies, including PARP inhibitors. Practice pattern questions pertaining to biomarker testing and the use of emerging therapies showed the majority of post-program respondents (42%) preferred to utilize blood/serum-based biomarker tests for their patient vs urine- or tissue-based tests. The greatest reported challenges to biomarker testing were affordability (30%) and lack of guideline clarity (23%). The top 2 barriers to adoption of new agents were reported as lack of awareness and lack of experience (32% and 20%, respectively). Conclusions: The activity successfully improved uro-oncology team knowledge of genetic testing and newer therapies to manage castration-resistant prostate cancer. Learners demonstrated significant improvements in competence concerning biomarker testing, treatment personalization, and adverse event management. Open-ended responses to behavioral impact questions illustrated improvements in biomarker usage, application of newer therapies, and confidence in patient counseling regarding treatment options.
Evidence for accelerated aging in mammary epithelia of women carrying germline BRCA1 or BRCA2 mutations
Authors: Sundus F. Shalabi, Masaru Miyano, Rosalyn W. Sayaman, Jennifer C. Lopez, Tiina A. Jokela, Michael E. Todhunter, Stefan Hinz, James C. Garbe, Martha R. Stampfer, Kai Kessenbrock, Victoria E. Seewaldt, Mark A. LaBarge
Journal: Nature Aging (2021)

Abstract During aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally expressed in myoepithelial cells. We hypothesize that loss of lineage fidelity is a general manifestation of epithelia that are susceptible to cancer initiation. In the present study, we show that histologically normal breast tissue from younger women who are susceptible to breast cancer, as a result of harboring a germline mutation in BRCA1 , BRCA2 or PALB2 genes, exhibits hallmarks of accelerated aging. These include proportionately increased luminal epithelial cells that acquired myoepithelial markers, decreased proportions of myoepithelial cells and a basal differentiation bias or failure of differentiation of cKit + progenitors. High-risk luminal and myoepithelial cells are transcriptionally enriched for genes of the opposite lineage, inflammatory- and cancer-related pathways. We have identified breast-aging hallmarks that reflect a convergent biology of cancer susceptibility, regardless of the specific underlying genetic or age-dependent risk or the associated breast cancer subtype.
Distinguishing Constrictive Pericarditis From Restrictive Cardiomyopathy—An Ongoing Diagnostic Challenge
Authors: John W. Hirshfeld, Hillary Johnston-Cox
Journal: JAMA Cardiology (2021)

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Patterns of virtual care among long-term cancer survivors.
Authors: Katherine Ramsey Gilmore, Patricia Hansberry Chapman, Guadalupe R. Palos, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2021)

335 Background: The recent pandemic led to an untypical demand for virtual care visits in our comprehensive cancer center. Our institution responded to this paradigm shift by offering virtual care to all cancer patients, including cancer survivors. In place of an in-person visit, patients were offered a live video or telephone (audio) appointment for their survivorship clinic visit. We conducted a quality improvement study to identify patterns in the type of virtual visits preferred by patients scheduled for appointments in eight dedicated survivorship clinics. Methods: We conducted a retrospective review of 4784 patients’ medical records who were seen in eight site-specific survivorship clinics from April 2020 – April 2021. Variables reviewed included type of visit, i.e. telephone, live video, or in-person, and patient characteristics such as age, gender, clinic, and distance from cancer center. Descriptive statistics were performed to assess for patterns of virtual care. The review was approved by the Quality Improvement Assessment Board. Results: Virtual care visits varied by clinic (0-86%). Five clinics ((breast, lymphoma, sarcoma, melanoma, and gynecological) performed &lt; 3% of visits using virtual format. A sub-analysis of the 8 clinics performing virtual visits demonstrates 59.5% virtual activity (19.23% phone compared to 39.3% video). Older patients were more likely to use any form of virtual visit compared to in-person (58.9% for those ≥ 65 vs. 54.9% for 18-39). Older patients were more likely to prefer phone visits (25.5% for ≥ 65 vs. 11.2% for 18-39). Local patients were more likely to utilize virtual visits (63% for patients &lt; 75 miles vs. 45% for patients &gt; 500 miles). Patients who lived furthest from the cancer center were more likely to travel in for their appointment, though this population contained fewer patients than those within 75 miles. Use of virtual visits for survivorship care varied, depending on the types of clinical diagnostic tests or examinations required for an annual visit. Conclusions: Our results indicate the use of virtual care was optimal when only lab testing was ordered by their provider. Older adults, with no or limited access to and knowledge of digital technology (computers, smartphones, and others similar tools) may need additional support to engage in video visits. Our findings suggest virtual care can be successfully implemented in the care of survivors. Further research would help determine best-practice approaches to facilitating patient engagement in virtual visits since telemedicine continues to evolve as a standard method to deliver safe and optimal cancer care.
Formation of a ZnO nanorods-patterned coating with strong bactericidal capability and quantitative evaluation of the contribution of nanorods-derived puncture and ROS-derived killing
Authors: Jing Ye, Bo Li, Mei Li, Yufeng Zheng, Shuilin Wu, Yong Han
Journal: Bioactive Materials (2021)

To endow Ti-based orthopedic implants with strong bactericidal activity, a ZnO nanorods-patterned coating (namely ZNR) was fabricated on Ti utilizing a catalyst- and template-free method of micro-arc oxidation (MAO) and hydrothermal treatment (HT). The coating comprises an outer layer of ZnO nanorods and a partially crystallized inner layer with nanocrystalline TiO2 and Zn2TiO4 embedded amorphous matrix containing Ti, O and Zn. During HT, Zn2+ ions contained in amorphous matrix of the as-MAOed layer migrate to surface and react with OH- in hydrothermal solution to form ZnO nuclei growing in length at expense of the migrated Zn2+. ZNR exhibits intense bactericidal activity against the adhered and planktonic S. aureus in vitro and in vivo. The crucial contributors to kill the adhered bacteria are ZnO nanorods derived mechano-penetration and released reactive oxygen species (ROS). Within 30 min of S. aureus incubation, ROS is the predominant bactericidal contributor with quantitative contribution value of ∼20%, which transforms into mechano-penetration with prolonging time to reach quantitative contribution value of ∼96% at 24 h. In addition, the bactericidal contributor against the planktonic bacteria of ZNR is relied on the released Zn2+. This work discloses an in-depth bactericidal mechanism of ZnO nanorods.
Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study
Authors: Matthew S Davids, Benjamin L Lampson, Svitlana Tyekucheva, Zixu Wang, Jessica C Lowney, Samantha Pazienza, Josie Montegaard, Victoria Patterson, Matthew Weinstock, Jennifer L Crombie, Samuel Y Ng, Austin I Kim, Caron A Jacobson, Ann S LaCasce, Philippe Armand, Jon E Arnason, David C Fisher, Jennifer R Brown
Journal: The Lancet Oncology (2021)
Patterns of first-line systemic therapy delivery and adoption of bevacizumab in advanced ovarian cancer in Ontario, Canada.
Authors: Shiru Liu, Wing Chan, Genevieve Bouchard-Fortier, Stephanie Lheureux, Sarah Ferguson, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2021)

292 Background: Initial treatment of epithelial ovarian cancer (EOC) consists of combination of cytoreductive surgery (CSR) and/or chemotherapy. Targeted therapies such as bevacizumab have shown to improve outcomes in a subset population with high-risk features. Real-world patterns of systemic therapy delivery in EOC in the modern era are not well understood. Our objective is to evaluate the patterns of first-line systemic treatment of advanced EOC in Ontario, focusing on adoption of bevacizumab, which was approved for use in 2016. Methods: We conducted a retrospective, population cohort study using administrative databases held at the ICES in Ontario, Canada. Patients diagnosed with non-mucinous EOC between 2014 and 2018 were identified from the Ontario Cancer Registry; early-stage disease was excluded. Information on systemic therapy was obtained from Activity Level Reporting and New Drug Funding Program databases. Provider of care (gynecologic oncologist vs medical oncologist) information was obtained from billing codes. Academic cancer centers were identified using validated systemic facility codes from Cancer Care Ontario. Statistical analyses include descriptive statistics, t-tests, and multivariable logistic regression using SAS. Results: Out of 4,680 cases diagnosed with EOC during the study period, 3,632 (77.6%) were considered advanced stage. Median age of cohort was between 65-70, and the majority had Charlson score of 1-2 (97%) and are urban (91.8%). A total of 3,181 (87.6%) patients underwent CRS and 2,722(74.9%) patients underwent chemotherapy. Of those who received chemotherapy, 1,259 (46.2%) received neoadjuvant chemotherapy, 1,012 (37.2%) received upfront CRS, and 451(16.5%) received chemotherapy only. The majority of chemotherapy was delivered by gynecologic oncologists (60.6%) and in academic cancer centres (61.7%). There was no significant difference in use of neoadjuvant chemotherapy between medical oncologists and gynecologic oncologists (p = 0.67). Only 53 chemotherapy patients (1.9%) received bevacizumab containing-regimen in the first-line setting. Medical oncologists were 4 times more likely to administer bevacizumab-containing regimen compared to gynecologic oncologists (OR 4.03, 95% CI.29 – 7.36) after adjusting for age, stage, Charlson score and rurality score on logistic regression. Delivery of bevacizumab is relatively higher in non-academic cancer centres (OR 2.61, 95% CI 2.32- 2.94) while 83% of intraperitoneal chemotherapy is delivered in academic cancer centres. Conclusions: Patterns of care of EOC in Ontario remain heterogenous between care providers and institutions, while uptake of bevacizumab for first-line treatment of EOC remains low. Factors leading to low uptake and real-world outcomes should be explored.