bluuebunny/crossref_metadata_2025 huggingface dataset:
A nomogram to predict the value of mammary adipose index (MAI) for prediction of response to neoadjuvant chemotherapy in breast cancer patients.
Authors: Xu Wenxiu , Tang Jinhai
Published: June 2021

e12607

Background: Breast cancer (BCa) is the most common malignancy in females on a global scale. Neoadjuvant chemotherapy (NACT) is a promising therapeutic approach for the treatment of locally advanced BCa, which result in primary tumor regression and optimal surgical planning. Cumulative evidence has identified a deleterious crosstalk between cancer cells and the surrounding mammary adipose tissue during tumor progression. Mammary adipose index (MAI) is a novel indicator defined by us, which represents the percentage of adipose tissue in breast. Therefore, this study aims to investigate the correlation between MAI and NACT efficacy of BCa by establishing an intuitive nomogram. Methods: Clinical data of 221 BCa patients who received NACT at the First Affiliated Hospital of Nanjing Medical University from January 1, 2018 to May 31, 2020 were retrospectively collected. Besides, patients were divided into major histological response and non-major histological response group in line with Miller-Payne pathology grading. The level of MAI was collected from magnetic resonance imaging of breast, and was divided into two groups according to the cut-off value. The level of MAI and clinicopathological characteristics were collected to assess the predictive roles of NACT response. Univariate analysis was performed by Chi-square test or Fisher’s exact test. Indicators with P < 0.05 were included in multivariate binary logistic regression analysis. The nomogram was constructed based on results of multivariate logistic analysis. The predictive accuracy and discriminative ability were evaluated by C-index and the calibration curve. Results: Among the 221 patients enrolled, 77 cases (34.84%) were represented by major responses of pathologic histology. In univariate analysis, the level of MAI, tumor size, node status, ER status, PR status HER-2 status and Ki-67 status were correlated with NACT. Multivariate Logistic regression analysis showed that tumor size, HER-2 status and the level of MAI were independent influencing factors for the response to NACT in BCa patients. The patients with a high level of MAI (≥0.6916) were more likely to have a worse NACT response. MAI was an independent predictor for NACT efficacy, and area under the curve of ROC, specificity and sensitivity of the predictive model were 0.805, 0.632 and 0.774 respectively. The nomogram established based on these factors showed its discriminatory ability, and the C-index for prediction was 0.881. The calibration curve indicated that the predictive ability of the nomogram was a good fit to actual observation. The difference was statistically significant (P < 0.05). Conclusions: The nomogram constructed in the present study indicated that the level of MAI could predict the efficacy of NACT in BCa patients, which might provide clinical guidance for the selection of appropriate treatment decisions.
Intra- and inter-observer variability in tumor infiltrating lymphocyte scoring in breast cancer core needle biopsy.
Authors: Geršak Klara , Gazic Barbara , Klevisar Ivancic Andreja , Ruzic Gorenjec Nina , Grasic Kuhar Cvetka
Published: June 2021

e12626

Background: Morphological evaluation of tumor lymphocyte infiltration (TIL) in breast cancer (BC) is gaining importance in the clinical setting, as it provides good prognostic information. Most institutions adhere to TIL working group guidelines for evaluating TIL, while having to settle on an acceptable error margin due to its subjective nature, which leads to intra and inter-observer scoring discordance. We aimed to analyze both at our institution, using experienced and inexperienced examiners, with a continuous variable scoring system. Methods: 209 BC core needle biopsy (CNB) samples were stained using hematoxylin-eosin. The percentage of stromal TIL was scored using a numerical variable ranging from 1 to 100. The examination group consisted of two experienced pathologists (pathologist A and B) and one inexperienced examiner - a medical oncology resident with a learning process containing study of the TIL working group analysis criteria and about 100 samples analysed together with an experienced pathologist Pathologist A and the resident analyzed the study samples twice, pathologist B once. Intraclass correlation coefficient (ICC) was used to measure overall intra and inter-observer agreement. Statistical analysis was performed using Google Sheets and Python. Results: 203 CNB samples were analysed (6 were excluded due to inadequate quality or an inconclusive diagnosis). Patients were aged 26 to 79 years (median 49). Sample size ranged from 1 to 16 mm (median 8). The proportion of BC subtypes was: luminal A-like 18%, luminal B-like 39%, HER2+ 10%, luminal B-like HER2+ 12%, TNBC 18%, not defined 2%. The highest proportion of high stromal TIL (≥50%) was seen in HER2+ (30%) and TNBC (22%) subtypes, as observed by pathologist A. We found good intra and inter-observer ICC (Table). Conclusions: Acceptable intra and inter-observer variability was observed in experienced pathologists, suggesting that the proposed methodology could reliably be used in clinical practice, research and trials. Interestingly, variability analysis of scores from a trained non-pathologist has also produced good results. However, it is important to note that inexperienced scoring could be prone to errors, for example counting non-lymphocyte cells as such, not recognizing regions of necrosis or sample damage, or not distinguishing between the tumor and peripheral stroma. Intraclass correlation: two-way random, single score (ICC2); pathologist A and resident (R) first and second analysis (A1, A2, R1, R2); pathologist B analysis (B1). Interpretation of ICC: <0.50 poor; 0.50-0.75 moderate; 0.75-0.90 good (0.75 = minimal acceptable value for a reliable clinical measurement); >0.90 excellent. Clinical trial information: 2018-000547-11. [Table: see text]
Australian real-world outcomes of ribociclib and aromatase inhibitor in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC): Results from Kisqali Access Registry for Metastatic breast cancer in Australia (KARMA) collected alongside a medicine access program.
Authors: Wong Vanessa , de Boer Richard , Baron-Hay Sally E. , Blum Robert helmut , Forster Benjamin Carl , Chua Susan Li Ling , Cuff Katharine , Green Michael , Lim Elgene , Mok Kelly , Nott Louise M. , Nottage Michelle K. , Tafreshi Ali , Tsoi Daphne T. F. , Yeo Belinda , Gibbs Peter , Lok Sheau Wen
Published: June 2021

e13018

Background: International guidelines recommend a combination of CDK4/6 inhibitor and endocrine therapy (ET) as first line treatment for HR+, HER2- MBC. Results from MONALEESA-2 demonstrate improved progression free survival (PFS) with ribociclib (CDK4/6 inhibitor) and ET as compared to ET alone. Prior to Australia’s Pharmaceutical Benefits Scheme funding, ̃800 patients participated in the ribociclib Medicine Access Program (MAP) from May 2017 to June 2018. Methods: KARMA is a secondary data use, non-interventional study of Australian patients who received first line treatment with ribociclib and aromatase inhibitor (AI), obtained via a MAP, for HR+, HER2- MBC. The aim was to capture comprehensive patient and treatment data to reflect real world practice and outcomes. Direct comparisons were made with the ribociclib/letrozole cohort in MONALEESA-2 given that the eligibility criteria were similar for both studies. Results: Data from 160 patients at 17 sites was analysed with a median follow up of 36.5 months. Baseline characteristics are shown in the table. 63 of 160 (39%) patients remain on ribociclib/AI at time of analysis. 58% of patients had at least 1 dose reduction, with the majority (77%) requiring only a single dose reduction. The most common reasons for dose reductions were neutropenia (68%) and abnormal liver enzymes (17%). 16 of 160 (10%) discontinued treatment due to toxicity, including 1 patient with QTc prolongation > 600ms. There were no deaths due to toxicity. Median duration of treatment and PFS were 24.5 (95% CI 17.8-33.3) and 36.3 months (95% CI 29.9- NR) respectively, compared to 20.2 and 25.3 months in MONALEESA-2. Landmark PFS was 76% at 12 months, 67% at 18 months and 64% at 24 months. Conclusions: This is the first real world study of ribociclib and AI developed alongside a MAP. The combination treatment was well tolerated with similar rates of dose reductions (58% in both) and treatment discontinuation due to toxicity (10% vs 8%) when compared to MONALEESA-2. This real-world cohort achieved a superior PFS, potentially explained in part by a younger population with more favourable baseline disease characteristics, including fewer disease sites and higher rates of bone only metastases. It is encouraging to see drug tolerability and efficacy replicated in real world patients.[Table: see text]
Impact of COVID19 pandemic on the hospitalization burden of cancer patients: Results of a quasi-experimental study.
Authors: Sanchez Juan Cristobal , Nuñez García Beatriz , Ruano Alberto , Blanco Mariola , Cantos Sanchez de Ibarguren Blanca , Mendez Miriam , Ramos-Vegue Arturo Jose , Morito Ana Maria , Aguado Ramon , Provencio-Pulla Mariano
Published: June 2021

e13527

Background: The SARS-CoV-2 (COVID19) pandemic has had a huge impact on health care, leading to the declaration of a “state of alarm” in many countries. This situation has possibly conditioned the care of cancer patients, compromising hospitalization resources due to healthcare restraints. We aim to analyze the impact of the COVID19 pandemic on the hospitalization of cancer patients during the “state of alarm” in an Academic Hospital in Madrid, considered one of the most affected regions in the World during the first wave of the pandemic in Europe. Methods: Quasi-experimental study with similar controls collected in the same period of the previous year from cancer patients admitted to the Medical Oncology (MO) department of the Puerta de Hierro University Hospital in Madrid. Patients were selected from diagnoses coded by the ICD-10 obtained from discharge reports in the Admission Department. Cancer and viral pneumonia codes (excluding influenza) were analyzed. Admission to Internal Medicine (IM) department was also explored to describe hospitalization due to COVID19 pneumonia. We defined two groups: pandemic (03/14/20 - 06/20/20) and control (pre-pandemic) (03/14/19 - 06/20/19). Results: 74 cancer patients were admitted to MO department in 2020, while 162 admissions were recorded for the equivalent period in 2019 (- 54%). No differences were observed related to sex and age. In 2020, emergency and programmed admissions decreased by the same proportion, and no difference in mortality was observed. Admissions for all neoplasms decreased, but with higher magnitude in breast cancer. Viral pneumonia (no influenza) in cancer patients were mostly admitted to IM (96%) rather than MO department. 79 cases were identified in 2020, 22 in 2019 (p < 0.001), with a non-significant increase in mortality in patients with pneumonia: 25,3% in 2020 and 13,6% in 2019. Conclusions: The COVID 19 pandemic seriously impacted cancer hospitalization care, decreasing admissions to the MO department in half compared to the equivalent period. We observed a reduction in admissions through all neoplasias. Admissions due to viral pneumonia in cancer patients increased 3.5 times, mostly admitted to IM changing the dynamics of cancer hospitalization burden and compromising resources. A non-significant increase in mortality from viral pneumonia was observed. The analysis of hospitalizations through administrative data can allow better management of resources and facilitate rapid decision-making in a pandemic situation yet to be resolved.[Table: see text]
Trends in modifiable behaviorally related cancers: Who is affected the most?
Authors: Chan John , Caesar Michelle Ann P. , Chan Chloe , Richardson Michael , Kapp Daniel Stuart , Francoeur Alex Andrea , Liao Cheng-I
Published: June 2021

e13531

Background: To examine trends in modifiable behaviorally related cancers among racial groups in the United States. Methods: Data were obtained from the United States Cancer Statistics (USCS) database for all cancers diagnosed between 2001 and 2017. Alcohol-associated cancers, HPV-associated, obesity-associated, physical inactivity-associated, and tobacco-associated were defined using ICD-O-3 site codes. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate the trends of associated cancers expressed per 100,000. Results: In women, the incidence of all cancers has decreased significantly or remain unchanged for all racial groups in 2017, with the exception of an increase of HPV related cancers in white women (APC = 0.77%, p < 0.001), obesity related cancers in Hispanic women (APC = 0.46%, p < 0.001), and postmenopausal breast cancer in Black and Asian women (APC 0.78%, 1.06%, p < 0.001). The incidence of alcohol, tobacco, obesity, and physical inactivity associated cancer decreased significantly in men for all racial groups in 2017. HPV related cancers increased annually by 3.13% (p < 0.001) in White men and 0.90% in Asian men (p = 0.022). The highest decrease in modifiable factors associated with cancers was in physical inactivity related cancers in black men from the west (APC = -3.79, p < 0.001). The intersection of black race and U.S. region had the highest decreases in all cancers except obesity-related cancers where the intersection of Asian race and Midwest region had the highest decrease. Conclusions: In women, most modifiable factors associated with cancer are decreasing except in obesity related cancers and physical inactivity/obesity related postmenopausal breast cancer. In men, these rates of cancer are decreasing for all racial groups except HPV related cancers in White and Asian men.
Patient quality criteria for a multidisciplinary integrated care pathway for von Hippel-Lindau syndrome.
Authors: Giles Rachel H. , Dreijerink Koen , van Leeuwaarde Rachel , Wolters Wendy , Zandee Wouter , Zondervan Patricia , Links Thera P. ,   Dutch VHL Working Group
Published: June 2021

e13534

Background: The objective was to establish a comprehensive set of patient-driven recommendations for specialists and allied healthcare professionals for the care of individuals with the multiple neoplasia syndrome von Hippel-Lindau (VHL). VHL patients require multiple surgeries during the course of their lifetimes, due to cysts and tumors in various organs including the kidney, brain, eye, spine, pancreas, adrenal glands, and broad ligament/epididymis. Screening and care from multiple specialists form the backbone of their care, yet this is rarely coordinated in an optimal manner. Methods: The Dutch VHL patient organization (Belangenvereniging VHL) initiated this process, and approached specialists and expert patients for input. Using components of consensus methodology, a 20-member multidisciplinary panel produced an integrated care pathway relating to the provision of care for VHL patients by patients, medical specialists, specialist nurses and allied healthcare professionals. Items were developed by 3 rounds of email correspondence in which the basis was formed for a consensus meeting which constituted the third round of review. The fourth and final round was an email review of the consensus output. Results: The panel agreed on recommendations for the optimal quality of care for VHL patients, in the form of a decision tree, which is supervised by a nurse specialist as a main contact point. These items were grouped under categories of "Diagnosis" and "Patient Pathway" and included recommendations on training, communication, and quality assessment as well as specific items related to VHL diagnosis clinics, non-academic treatment clinics, and follow-up survivor groups. The Netherlands has 3 official Expert Reference Centers for VHL care (Groningen, Utrecht, Nijmegen), and the patient organization and allied specialists are planning to publish this protocol, while implementing its practice in those 3 sites. Conclusions: Medical specialists (internists, endocrinologists, urologists, neurosurgeons, ophthalmologists, geneticists, etc) and specialist nurses play a vital role alongside allied healthcare professionals to provide care to people with VHL and their families. Yet VHL patients and their families are the experts most acquainted with their own unmet needs. We present a set of standards and consensus recommendations from the patient perspective for the roles for these practitioners to provide optimal VHL care. These recommendations could form the basis for facilitated development of comprehensive integrated pathways for any pleiotropic neoplasia syndrome, and represent best-practice collaboration between patient organizations and national expertise centers to provide value-based healthcare.
Distress screening for patients with a history of cancer during the COVID-19 pandemic.
Authors: Worster Brooke , Waldman Lauren , Garber Gregory D. , Dahal Subecha , Binder Adam F , Csik Valerie Pracilio , Handley Nathan , Gentsch Alexandra , Rising Kristin , Trachtenberg Olivia , Lopez Ana Maria
Published: June 2021

e13537

Background: Although a diagnosis of cancer is widely accepted as resulting in significant levels of distress, distress itself cannot be considered benign and screening for distress is considered a best practice metric for patients receiving oncological care. Endorsed by NCCN, the Distress Thermometer (DT) considers a cutoff score of 4 or greater to identify patient with clinically relevant levels of distress. We hypothesized that the COVID-19 pandemic would manifest with higher levels of stress and anxiety in most persons by compounding the distress experienced by patients with a diagnosis of cancer. Methods: Patients with a new diagnosis of cancer underwent distress screening with the DT prior to a clinical appointment at a NCI-designated academic cancer center. Patients who scored 4 or higher were discussed at an Interprofessional Supportive Medicine patient conference or referred to oncology social work for appropriate evaluation and therapeutic care. By mid-March 2020, the SKCC catchment area was under a public health emergency with limited access to non-essential healthcare; therefore, we present data from 1/1-3/15/20 (pre-pandemic), 3/16-6/7/20 (pandemic peak with 2000+ daily cases in late April and peak daily deaths 300+ in May), and 6/8-8/30/20 (daily cases generally less than 700 except for occasional levels of 1000-in July and daily deaths less than 40 daily). Results: In the pre-pandemic time period, 60% of patients assessed reported a score of 4 or higher. During the subsequent periods—the first pandemic peak and the first post-pandemic period—the incidence of an elevated distress screen (4 or higher) was relatively stable at about 30%. Conclusions: Contrary to expectations, the DT screen identified less patient distress during the pandemic compared to pre-pandemic. Our results may be due to multiple factors—changes in processes and procedures to prioritize DT screening as pandemic risk became more apparent; an increased use of telemedicine; and the compounding of new, non-cancer related stressors resulting in the greater resiliency noted in disaster psychology. For example, during the first pandemic peak when the majority of patients were seen via telemedicine, the opportunity afforded by telemedicine for safety and decreased risk for COVID-19 infection may have reduced the overall distress experience. In addition, the compounding of stressors—the diagnosis of cancer, the risk of the pandemic, and its economic and financial stressors—may have influenced distress perception. Future work incorporating multiple distress assessment points may help better understand the impact of the layers of stress experienced by persons with cancer.[Table: see text]
Oncology clinical research landscape in Middle East and North Africa (MENA) region: Challenges and proposed solutions.
Authors: Sameh Kareem , Khalife Natasha
Published: June 2021

e13567

Background: Similar to other regions of the world, cancer incidence in Middle East and North Africa (MENA) is rising, which has been attributed to increased life expectancy and adoption of western lifestyle habits. Conducting clinical trials in the region is important to assess efficacy and safety of oncology medications in the specific population (response to drugs can be impacted by genetics, demographics and lifestyle factors). Although the MENA comprises around 5% of the global population, the region only participates in approximately 3% of clinical trials worldwide. It is important to understand the challenges in conducting trials in MENA and identify strategies to overcome these in order to facilitate advances in clinical research in the region. Methods: A literature review was conducted (via e.g. PubMed and ClinicalTrials.gov) to understand the current oncology clinical research landscape in MENA (from Jan 2015-Dec 2020), with the aim of identifying key challenges and potential strategies to overcome these. Results: Conduct of oncology clinical trials (phases 1-4) has risen in recent years in MENA, from 47 trials in 2015 to 53 trials in 2020. Despite the presence of various research-favourable factors in MENA (large patient pool, high demand for medication, lower clinical trial operational costs, compliance with ICH-GCP standards), the region still falls behind other countries in clinical research. Key factors identified as challenges in conducting clinical trials in MENA include the research infrastructure and patient awareness/understanding of research. We propose the following strategies to support the advancement of clinical research in the region: (1) Enhance research infrastructure through bolstering national clinical research networks and supporting collaboration between healthcare institutes, academia and the pharma industry; (2) Diversify methods of patient engagement (e.g. patient advisory groups and social media networks) and provide education on pros/cons of participating in research to raise awareness and improve trial participation rates; and (3) Improve availability of comprehensive oncology registries to enhance understanding of disease burden and support clinical research. Conclusions: The conduct of oncology clinical trials in MENA is increasing, yet the region is still under-represented in the global clinical trial market, despite its significant potential. The advancement of clinical research in the region will require a multi-level approach, involving collaboration between multiple stakeholders including the pharma industry, regulators, government, and healthcare professionals.
A prospective study of an AI-based breast cancer screening solution for resource-constrained settings.
Authors: Bansal Richa , Aggarwal Bharat , Krishnan Lakshmi
Published: June 2021

e13586

Background: Screening mammography is often found to have low sensitivity in women with high density breast tissues. Alternate modalities of breast USG and MRI require high-quality expensive equipment making the regular screening with these modalities less affordable and accessible, particularly in resource-constrained settings This study evaluates the clinical performance of an AI-based test (Thermalytix) that uses machine learning on breast thermal images which could potentially be a low-cost solution for breast screening in low- and middle-income countries (LMICs). Methods: The prospective comparative study conducted from December 2018 to January 2020 evaluated the performance of Thermalytix in women with dense and non-dense breast tissue who presented for a health check-up at a hospital. All women underwent Thermalytix and mammography. Further investigations were recommended for participants who were reported as positive on either test. Sensitivity and specificity of Thermalytix were evaluated across age-groups, menopausal status, and breast densities. Results: Among the 687 women recruited for the study, 459 women who satisfied the inclusion criteria were included in the analysis. 168 women had ACR categories ‘c’ or ‘d’ dense breasts, of which 37 women had an inconclusive mammography report (BI-RADS 0). Overall, 21 women were detected with breast cancer in the study. Thermalytix demonstrated an overall sensitivity of 95.2% (95% CI, 76.1-99·9) and a specificity of 88.6% (95% CI, 85.2-91.4). Among women with dense breast tissue (n=168), Thermalytix showed a sensitivity of 100% (95% CI, 69.2-100) and a specificity of 81.7% (95% CI, 74.7-87.4). In women with ACR categories ‘c’ and ‘d’ dense breasts, mammography reported 22% of them as inconclusive (BI-RAD 0), while in the same sub-set of the population Thermalytix demonstrated a sensitivity of 100%. Conclusions: The AI-based Thermalytix demonstrated high sensitivity and specificity in the study cohort. It also fared well in women younger than 50 years and pre-menopausal women where routine mammography screening yields low sensitivity. Overall, this study introduces Thermalytix, a promising radiation-free, automated, and privacy-aware test that can supplement mammography for routine screening of women, especially in women with dense breast tissue, and has the potential to influence the clinical practice in LMICs by making breast cancer screening portable and affordable. Performance of Thermalytix and mammography in women with high breast densities (ACR categories ‘c’ and ‘d’ breasts). Clinical trial information: NCT04688086. [Table: see text]
Cancer Care during Covid-19: A multi-institutional qualitative study on physician and patient perspectives on telemedicine.
Authors: Wong Bonnie O. , Aslakson Rebecca , Holdsworth Laura M , Siden Rachel , Tabor Holly , Verano Mae-Richelle , Schapira Lidia
Published: June 2021

e13611

Background: The COVID19 pandemic has had significant effects on cancer care, including disruptions or delays to screening, diagnosis, treatment, and follow-up for cancer patients as well as shifts from in-person visits to telemedicine to allow for continued access to care. Methods: We conducted semi-structured in-depth interviews with fifty radiation oncologists, medical oncologists, surgical oncologists, and cancer patients or their caregivers. These physicians and patients were recruited from four different hospitals in varying geographic regions and of varying practice settings. Interviews were conducted between October 2020 and May 2021. Interviews were transcribed, then thematically coded to consensus by three researchers. Results: The COVID19 pandemic shifted cancer care from in-person visits towards telemedicine. Providers recognized the necessity and benefit of telemedicine in increasing access to care, but were generally dissatisfied with use of telemedicine. These reasons included: (1) difficulty conducting physical exam maneuvers and assessing patient status; (2) technological failures, exacerbating barriers to care; (3) absence of “connection” with patients; (4) decreased access to interdisciplinary care teams. Patient perspectives on telemedicine were similarly varied, but were overall positive. Patients appreciated the convenience of accessing telemedicine at home, particularly for those who travel long distances or have difficulty traveling. Patients cited challenges similar to their physicians: technological difficulties and the loss of human connection usually conveyed through touch and physical presence. Conclusions: Telemedicine has been a key tool to allow for continued access to care and may continue to be a visit modality after the pandemic subsides. However, telemedicine poses numerous challenges for both physicians and patients and creative solutions to allow for “human connection” via telemedicine should be sought. Further evaluation is needed to determine the effect of telemedicine on quality of care.
Teleoncology: Assessing online communication skills of millennial medical students.
Authors: Gil Deza Ernesto , Gil Deza Lourdes , Abal Mariana , Dragosky Marta , Acuna Claudia Lorena , Marin Ordoñez Alba , Montiel Monica , Tognelli Flavio A , Smolje Leonel , Gonzalez Cesar , Brandon Maximiliano , Garcia Gerardi Carlos , Martin Reinas Gaston , Ares Sandra L. , Gercovich Daniela , Rivarola Edgardo G. J. , Morgenfeld Eduardo L. , Gercovich Felipe G. ,   IOHM-USAL-ECOE 2020
Published: June 2021

e13616

Background: COVID-19 posed new challenges in patient care and led to an increase in teleoncology. This paper analyzes telemedicine communication skills of millennial medical students of the postgraduate program of Clinical Oncology at Universidad del Salvador, Buenos Aires. Methods: Student assessment was based on a video call interaction with simulated patients in two stations (30 minutes each) of the Virtual Observational Standard Clinical Examination (V-OSCE), implemented in November 2020. Students received virtual communication guidelines and participated in training sessions to use the video call platform. All interactions were recorded. Assessment items (Table). Results: A total of 25 students were evaluated: 1 (4%) was ineligible due to network connection issues; 24 (96%) participated in both interactions. We analyzed 48 interactions in total. Opening: 6/48 interactions completed all five required items. Most recurring problems: not checking for patient’s previous experience with teleoncology (37/48) and not providing an alternative communication channel in case of technical difficulties (40/48). Middle: the results were similar to in-person interaction observed in previous exams, 35/48 interactions completed all required items. End: 16/48 interactions completed both items. In 32/48 the student did not check for patient understanding of the information provided. Only 3/48 interactions completed all 12 items. Conclusions: A) The V-OSCE is a useful tool to practice and evaluate teleoncology communication skills. B) The Middle Moment of the interactions was similar to an in-person interaction. However, the Opening and End of the interview were more challenging. The most critical struggles being: checking for patient’s previous experience in teleoncology, providing an alternative communication channel in case of technical difficulties and checking for patient understanding. C) COVID-19 established new forms of communication that are likely to remain even after the pandemic has ended. It is important to address this demand for online communication skills in medical education curricula.[Table: see text]
A prognostic model based on CGGA and TCGA databases for predicting outcome of glioma patients.
Authors: Ni Hongbin , Zhang Xing , Wang Xiaoxuan , Song Chao
Published: June 2021

e14017

Background: Glioma is the most frequent primary malignance of the central nervous system (CNS) and causes the top-ten deaths of cancers. Isocitrate dehydrogenase ( IDH) mutations and chromosome 1p and 19q codeletion are the known prognostic factors of glioma. However, it is still not enough to predict the outcomes. Herein, we conduct a prognostic model of patients with gliomas. Methods: The Chinese Glioma Genome Atlas (CGGA) contained 286 patients with whole-exome sequencing (WES) was used to established the model. Kaplan-Meier analysis based on log-rank test was used to confirm the single mutation overall survival (OS) factors (allele frequency≥ 5) in CGGA. The model was established based on the Cox regression of above significant factors. The data of 1122 patients with glioma in TCGA (The Cancer Genome Atlas) was used to validate the model. Results: According to the CGGA database, the OS factors of glioma patients were 1p/19q, CIC, EGFR ( p< 0.001), IDH1, IRS2, NF1, NOTCH1, PDGFRA, PTEN, ROS1, SMARCA4 and TP53. The Cox regression revealed 1p/19q codeletion (HR = 2.008, 95%CI 1.397-2.885, p< 0.001), EGFR (HR = 0.420, 95%CI 0.217-0.811, p= 0.010), PDGFRA (HR = 0.271, 95%CI 0.139-0.528, p< 0.001), and ROS1 (HR = 0.197, 95%CI 0.071-0.549, p= 0.002). Based on the β value of the regression equation, we divided the glioma patients into 3 groups (G1: harboring EGFR, PDGFR and/or ROS1 mutations; G2: wide type; G3: harboring 1p/19q without mutations in three genes). In TCGA, the OS of glioma patients was also showed G1 < G2 < G3 significantly. Conclusions: The prognostic model was divided glioma patients into three groups reasonably and could provide new reference for the glioma management. It needed to be further verified in more cohorts.
Measurement of treatment dependent glioblastoma cell density in T1- weighted contrast enhancement at autopsy.
Authors: Lowman Allison , Bobholz Samuel , Connelly Jennifer Marie , Cochran Elizabeth , Mueller Wade , Brehler Michael , Kyereme Fitzgerald , Sherman John , Duenweg Savannah , LaViolette Peter S
Published: June 2021

e14035

Background: With an average overall survival of 12-18 months, glioblastoma has a particularly grim diagnosis. Standard treatment of glioblastoma, following detection on MRI, is surgical resection followed by radiation therapy and chemotherapy and is monitored through MR imaging. Glioblastoma has a unique heterogenous nature that complicates visualization of subtly enhancing tumor. This study used autopsy tissue samples taken from glioblastoma patients with varying treatment, to examine the effects of treatment on cell density within regions of contrast enhancement, using T1-weighted subtraction maps (T1S) from the last MR images to death. Methods: Eight patients diagnosed with glioblastoma at autopsy were recruited for this study. Two patients had no treatment and six received a combination of chemo-radiation and other treatments, including but not limited to bevacizumab (Bev) and TTFields therapy. At autopsy, whole brain samples were sliced axially aligned to the patient’s final MRI to death. Time between last MRI and death ranged from 4-27 days (mean 16 days). Overall survival (OS) ranged from 4-538 days (mean 307 days). Large tissue samples were taken from regions of suspected tumor or treatment effect, for a total of 18 tissue samples. Tissue samples were processed, H&E stained, and digitized at 40X resolution (Huron Slide Scanner). Cell density (cells/mm2) was calculated using digital histology. T1S were created for each patient by subtracting intensity normalized T1 weighted images from T1 post contrast images (T1C). Digital histology was aligned and resampled into MRI space using manual control point registration. Mixed effect models were used to compare differences in cell density across contrast enhancement (T1SE vs. NE) as well as across treatment groups (treatment vs. no treatment). Results: Cellularity was compared across regions of T1S enhancement (T1SE) and non-enhancement (NE) within manually selected regions of interest. Cell density compared between regions of T1SE and NE was not different (p=0.219). Total cell density was increased in patients who had received treatment compared to no treatment in both regions of T1SE and NE (p=0.014). Conclusions: Overall, cell density was increased in patients who had received treatment after diagnosis of glioblastoma. Additional research is needed to examine the extent of treatment’s effect on cellularity of glioblastoma. This work begins to characterize the use of T1S in evaluating glioblastoma tumor burden in patients with varying treatment histories.[Table: see text]
High-grade glioma of central nervous system: Single center treatment experience.
Authors: Olgun Nur , Kızmazoğlu Deniz , Özdoğar Batuhan , Çeçen Emre , Kızmazoğlu Ceren , Akyol Sefika , Demiral Ayşe , Çetingöz Rıza , Önal Ayşe , Uçar Handan Güleryüz , Özer Erdener , İnce Dilek
Published: June 2021

e14040

Background: To evaluate characteristics and treatment responses of patients with high grade gliomas (HGG) in our center Methods: Medical files of patients with malignant CNS tumors between 1987-2020 were analyzed retrospectively. There were 44 patients with HGG. Results: Diagnosis of patients as follows: 21 pons glioma, 2 anaplastic astrocytoma, 11 anaplastic ependimoma, 7 glioblastoma multiforme, 1 glioblastoma, 2 gliomatosis cerebri. The median age at diagnosis was 6,5 yrs (7 – 17 yrs), M/F:25/19. Age distrubution: <5 yrs 12 patients, 5-10 yrs 18 patients, 10-18 yrs 14 patients. The most frequent complaints for pons gliomas: cranial nerve paralysis (52%), visial impairment (48%), headache (38%), power loss (43%) and speech disorder (30%). Surgery was performed to extrinsic component of mass in 3 patients of pons gliomas. For other HGG: 7 subtotal resection and 16 gross total resection had performed. Seven patients died before RT. And other 37 patients received radiotherapy. RT total doses varied between 50-60 Gy. Seven patients were not received chemotherapy, 3 of them died before chemo, and others received only RT. Chemotherapy protocoles were changed over the years: For pons gliomas, MOPP (Mechlorethamine, vincristine, prednisone, procarbazine) in 3 patients, NOPP (nitrosourea, vincristine, prednisone, procarbazine) in 2 patients, only ICE (Ifosfamide, carboplatin, cisplatin) in five patients, oral cyclophosphamide in one patient, temozolamide in one patient and temo + bevacizumab in one patient. Last 3 patients received nimotuzumab-vinorelbine after ICE and temo. For other HGGs, platin based regimens used fort he first line treatment. Temozolamide-bevacizumab, irinotecan-temsirolimus combinations were the other options as second and also third line treatments. Median progression free survival time was 6 mos (2 weeks -25 mos) for pons gliomas, for other gliomas median progression free survival time was 14 mos (0 -74 mos). For pons gliomas: Event free survival rate for 6 mos was 75%, for one year was 17%, One year, 18 mos, and two years overall survival rates were 84%, 52% and 10% respectively. For other HGGs: Event free survival rate for one year and two years were 57% and 17% respectively. One year and two years overall survival rates were 73% and 36% respectively. Conclusions: High grade glioma is a group of tumor in which still the helplessness experienced in treatment. Despite radiotherapy and chemotherapy, prognosis is very poor. The progression free and overall survival rates of patients were similar to literature. With new developments in molecular pathology, as the use of molecular target therapies, the progression free survival rates newly will improve.
Optic glioma in children: Turkish experience.
Authors: Yaman Bajin Inci , Korones David Nathan , Aydin Burca , Karli Oguz Kader , Kurucu Nilgun , Yalcin Bilgehan , Varan Ali , Kutluk Tezer
Published: June 2021

e14042

Background: Optic gliomas are the most common tumors of the optic pathway, comprising about 1% of all intracranial tumours. Here we present the clinical characteristics and the outcome of patients with optic glioma at our institution. Methods: Seventy two patients diagnosed and followed up at a pediatric cancer center in Ankara, Turkey between January 1, 2008 and December 31, 2020 were included in this analysis. The clinical features and outcome of patients were recorded from patient files and hospital information system retrospectively. Results: The median age at the time of diagnosis was 3.5 years (4-157 months), the female/male ratio was 1.3. Fourteen children (19%) were asymptomatic and tumors were detected with routine surveillance, and 58 (81%) had symptoms (the most common being proptosis in 16 patients (22%)). The most common site of optic glioma was the intraorbital region (31%). Fourty patients (55%) had neurofibromatosis type 1 (NF-1). Five patients had histopathological diagnoses; 3 pilomyxoid astrocytoma, 2 pilocytic astrocytoma. Children were treated if they had tumor progression on MRI and/or worsening visual acuity. Twenty seven (38%) children were observed without any therapy, 6 patients (8%) received radiation and chemotherapy, 4 patients (5%) received radiation only, and 35 patients (49%) received chemotherapy only. Treatment regimens for the 41 children who received chemotherapy included carboplatin/etoposide (17), cisplatin/etoposide (18), carboplatin/vincristine (5), and temozolomide (1). The 5-year progression-free survival (PFS) and overall survival (OS) were 64% and 90%, respectively with a 31 month median follow-up. The 5 year PFS was significantly lower in patients with optic tract-hypothalamic-chiasmatic involvement (34%) than orbital involvement (83%) (p=0.013). Five year PFS was significantly higher in patients with NF-1 (80%) than patients without NF-1(46%) (p=0.027) and significantly lower in patients diagnosed at <3 years old (37%) (p=0.05). Five patients died of disease, and one died of infection after chemotherapy. Two patients treated with platin (1 carboplatin, 1 cisplatin) developed ototoxicity. One patient with NF-1 developed Moya-Moya disease. Two patients developed multiple pituitary hormone deficiencies and one patient developed precocious puberty during follow-up. No secondary malignancy was observed. Conclusions: The management of optic glioma remains challenging. Although the overall survival for children with this disease is excellent, progression of disease is frequent, particularly in those children without NF-1, younger children and non-orbital tumors. This study from Turkey showed comparable results with high-income countries. Further studies with longer follow-up periods are needed to find appropriate treatment strategies.
The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia.
Authors: Ding Xingchen , Yu Jinming , Hu Man
Published: June 2021

e14043

Background: Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it also increases PD-L1 expression in intracranial tumor is still unknown. Here we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. Methods: Tumor tissues from 120 patients with glioma, were analyzed for PD-L1 and HIF-1α expression using immunohistochemistry. And results were verified in vitro, using U251, U343 glioma cell lines. Gene expression were evaluated by quantitative PCR; protein levels were analyzed by Western blot; ChIP-qPCR (chromatin immunoprecipitation coupled with quantitative PCR) analysis showed the relationship between HIF-1α and PD-L1. Glioma in situ model were used to explore whether HIF-1α inhibitor (PX-478) can enhance anti-PD-L1 therapy responses. Tumor volume was measured twice weekly. Immune data were further analyzed by FACS DIVA 7.0 or Flow Jo 7.6.5 software. Results: In glioma patients, HIF-1α and PD-L1 were markedly overexpressed in high grade glioma (HGG) tissues and were both associated with poorer overall survival(OS) (PD-L1( < 5% vs. ≥ 5%): 3, 5, 10-year OS: 78.1%, 50.5%, 27.2% vs. 45.4%, 11.8%, 0%, P = 0.0026; HIF-1α( < 1% vs. ≥ 1%): 3, 5, 10-year OS:74.2%, 66.8%, 53.4% vs. 61.6%, 21.0%, 0%, P = 0.001). And the expression of PD-L1 was significantly positively correlated with the expression of HIF-1α in glioma patients ( r = 0.412, P < 0.001). In glioma cell lines, PD-L1 expression was significantly induced under hypoxia condition, but the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter, providing evidence that HIF-1α up-regulate PD-L1 expression in glioma cells. In glioma murine model, combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to mice treated with either single agent. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Conclusions: Multiple findings demonstrated that positive relationship between HIF-1α and PD-L1 existed in glioma cells under hypoxia condition. These observations also provide invaluable information that hypoxia contributes to a key phase of glioma cells evading adaptive immunity, thereby promoting malignant progression and poorer clinical outcomes. Given these, it would be a potential strategy to target HIF-1α in combination with the blockage of PD-1/PD-L1 pathway for anti-cancer in the future.
Landscape of hyper-progression related gene alterations among Chinese population and their impact on patients’ survival after immunotherapy.
Authors: Fu Wenfan , Li Si , Xi Wenjing , Yang Qidong , Chen Dongsheng , Xiao Mingzhe
Published: June 2021

e14518

Background: Immune checkpoint inhibitors (ICIs) have demonstrated salutary anticancer effects in patient with cancer. However, more than 10% of treated patients had experienced hyper-progressive disease (HPD), which resulted poor survival. Gene alterations might be associated with HPD, while more studies are needed to clarify their impact on survival and role in tumor progression. Methods: In this analysis, we retrospectively reviewed genomic alterations in 1814 Chinese patients with cancer of lung, liver, colorectal, gastric, pancreatic, biliary duct, melanoma, cervical and esophagus. Next-Generation Sequencing (NGS) by a customized 539-gene panel was performed. Frequency of HPD gene alterations, including amplification of MDM2/4, CCND1 and FGFR3/4, loss of CDKN2A/B, mutations in DNMT3A were investigated. Their impact on progress-free survival (PFS) after immunotherapy were further explored in lung cancer in Rizvi et. 2018 cohort. Results: Of 1814 patients, 449 (24.8%) harbored at least 1 HPD related gene alterations. Esophagus cancer (7/12,58.3%), melanoma (10/23, 43.5%) and liver cancer (108/268, 40.3%) took the largest proportion. The frequencies for each gene were CDKN2A loss (8.5%), CDKN2B loss (8.1%), DNMT3A mutation (7.8%), MDM2 amp (4.9%), MDM4 amp (3.8%), CCND1 amp (3.2%), FGFR4 amp (0.6%), FGFR3 amp (0.3%), respectively. Significant higher TMB in altered group was revealed in EGFR/ALK negative lung cancer (5.88 mut/Mb vs. 2.84 mut/Mb (wild group), P= 0.001). In Rivzi et. 2018 cohort, 46/240 (19.2%) patients had related gene alterations. The TMB was comparable between altered and wild-type groups. Median PFS were 2.5 months and 3.8 months for altered and wild-type group ( P= 0.074). Among altered patients, 17.4% achieved PFS > 6 months (Table 1), two of them had a 1-year PFS (1 with CDKN2A&B loss, 1 with DNMT3A). Conclusions: A considerable proportion of patients harbored HPD related gene alterations. Although they tend to present poorer PFS, there’re patients had the PFS>12 months, the exact impact and underline mechanisms requires more evidence. Distribution of progression-free survival (PFS) for each gene.[Table: see text]