bluuebunny/crossref_metadata_2025 huggingface dataset:
KANSURVIVE: Testing a telementoring model for improving cancer survivorship care in rural practice.
Authors: Klemp Jennifer R. , Knight Catie J. , Ellerbeck Edward F. , Befort Christie A. , Nelson Eve-Lynn , O'Dea Anne , Chalise Prabhakar , Hughes Dorothy , Greiner Allen
Published: July 2024

e13791

Background: Cancer survivors require long-term, coordinated care to address the physical, emotional, and psychosocial effects of cancer and its treatment. KanSurvive, a single arm feasibility trial, evaluated the effectiveness of the KanSurvive ECHO intervention combined with practice facilitation (PF) to promote better adoption of evidence-based practice (EBP) survivorship care guidelines for breast, colorectal, lung, and prostate cancer among rural survivors. Methods: Fifteen primary care clinics in Kansas (80% in RUCA codes 4-10), including 62 healthcare professionals, were invited to participate in four, 1-hour Project ECHO telementoring program held in 2021. Real-time videoconferencing sessions covered EBP survivorship guidelines for breast, colorectal, lung, and prostate cancer. Clinics used brief plan-do-study-act cycles with PF supporting implementation of the quality improvement process. Utilizing the National Quality Forum framework, a performance indicator booklet with established measures in preventive health and cancer survivorship was developed as a data collection and quality improvement resource. Performance indicators included EBP screening actions related to cancer surveillance, lifestyle factors, distress, evidence of a review of family history of cancer, and the patient’s cancer diagnosis documented in the EHR. Results: Three clinics (7 = healthcare professionals) withdrew from the project citing competing demands and a provider leaving the practice. The COVID-19 pandemic delayed project initiation and prevented clinic visits. Recruitment and study procedures were implemented remotely. Clinic staff identified 138 cancer survivors (M = 13, IQR [6-16] per practice) seen in the year pre-intervention, and 129 survivors in the year prior to post-intervention. Pre-intervention, overall tumor surveillance was 91%, but lung cancer surveillance was lower than other tumor types at 70%. Other than surveillance, measures of baseline performance were similar across tumor types: screening for distress 84%, assessment of BMI 97%, screening for tobacco use 83% and documentation of family history 70%. Post-intervention performance indicators were similar except for documentation of family history which increased to 89% (p < 0.01). Conclusions: Standardized survivorship metrics can facilitate quality assessment as part of an ECHO-based cancer survivorship program. Although there are modest opportunities for improvement, PCPs in this study caring for rural patients perform reasonably well across a variety of cancer survivorship performance metrics comparable to national primary care quality measures. Documented assessment of family history of cancer lags other metrics and improved after participation in the KanSurvive telementoring program.
Mapping models of care for children, adolescent and young adult cancer survivors: A scoping review.
Authors: Nekhlyudov Larissa , Bradford Natalie , Thamm Carla , Skrabal Ross Xiomara , Chan Ray
Published: July 2024

e13793

Background: Young cancer survivors, with decades of life ahead, encounter substantial risks for treatment-related late effects. Achieving optimal outcomes requires a comprehensive multi-dimensional approach. This scoping review aimed to systematically map the evidence on models of survivorship care for Child (0-14) and Adolescent and Young Adult (AYA, 15-39) cancer survivors aligning with the Framework for Quality Cancer Survivorship. Methods: Conducted according to PRISMA extension for scoping reviews, this study systematically searched MEDLINE, CINAHL and Embase for English articles from Jan 2006 to Jan 2024. Inclusion criteria were studies describing patient and health service domain for Child and AYA cancer survivorship models of care. Dual processes were used for article screening, selection, and data extraction. A deductive analysis, using Content Analysis informed results, presented in a narrative synthesis. Results: Of the 5,298 records screened 38 described Child and 10 described AYA models of care. The majority were cohort and cross-sectional studies from the USA, Canada, and the UK representing 6,101 Child and 5,283 AYA cancer survivors. Across these diverse studies, a broad range of outcomes were identified with most domains of the Framework represented. No model of care described more domains than another. Across the 13 possible elements of care and outcomes, most (68%) reported on less than five of these. The domains most represented included elements of care rather than outcomes at the service level such as the clinic structure (52%), communication and decision making (52%) and patient/carer satisfaction (50%). At the patient level, quality of life outcomes and assessment and management of physical symptoms were represented in 40% of studies. There were few studies reporting on health promotion (23%), chronic conditions (13%), mortality and healthcare utilization (5% each) and none reported on costs. In terms of outcomes, oncologist long-term follow up care showed higher adherence to risk-based recommendations compared to primary care models in some studies. Other studies suggest a shared care model increases adherence and decrease lost to follow-up. At the service level, high satisfaction with care was common in all models. Overall, there was not enough to evidence to support one model over another in either Child or AYA survivorship care. Conclusions: Despite decades of research in survivorship care, there is not enough evidence about the effectiveness and efficiency of different models of care. No single model stands out as superior, and there are notable gaps in understanding the economic and value proposition of different models. Addressing these gaps is crucial for the future development, and provision of quality survivorship care tailored for this patient population.
Time to treatment and follicular thyroid cancer survival: A SEER database analysis.
Authors: Cogua Laura , Tupper Connor , Silberstein Peter T.
Published: July 2024

e13794

Background: Follicular thyroid cancer (FTC) is a prevalent endocrine malignancy, typically managed with surgical resection. Few studies have investigated the optimal time of surgery for FTC at a national registry level. The aim of this study is to examine the impact of delaying surgical intervention on survival in FTC. Methods: Patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with FTC between 2000-2020 were selected. Additional variables were collected including age, sex, race, stage, surgical status, radiation status, time to treatment, household income, and population size. Kaplan-Meier, and one- and five-year logistic regression analyses were performed. Results: A total of 10,478 patients were included of which 95.5% underwent surgical management. There was a 98.3% and 96.4% survival rate at one- and five-years, respectively. On Kaplan-Meier, those who underwent surgery survived longer (p<0.001). Additionally, patients treated within one month of diagnosis survived significantly better than those treated later (p<0.001). On one-year logistic regression, higher staging was associated with worse survival while those who received surgery, radiation, and lived in counties with a median household income >$75,000 had better survival (p’s<0.05). On five-year logistic regression, patients older than 50 years old and higher staging were associated with worse survival while those who received surgery had better survival (p’s<0.001). No differences were observed for time to treatment at one or five years. Conclusions: Our results show that surgical management is associated with improved survival in patients with FTC. On univariate analysis, a duration of one month or less between diagnosis and treatment was associated with improved survival. However, on multivariate analysis, only surgical management, radiation, and median household income >$75,000 were associated with improved survival.
Understanding and comparing the views of specialty care providers and PCPs on addressing cancer survivorship needs via survivorship care plan portal.
Authors: Haggstrom David Andrew , Swaminathan Manasa , Donnelly Claire E , Cottingham Ann H. , Vachon Eric , Faidley Micah T.
Published: July 2024

e13799

Background: Individuals with colorectal cancer (CRC) experience persistent and disabling symptoms across the care trajectory. Consequently, Survivorship Care Plans (SCPs) have been developed to assist patients in navigating these experiences. However, there are mixed results regarding its effectiveness and implementation in helping cancer survivors. The purpose of this qualitative study is to explore and compare the attitudes of cancer specialists and PCPs on current practices for survivorship care coordination, and to identify potential barriers and facilitators to implementing a SCP-PHR tool. Methods: Semi-structured interviews were conducted with 22 providers involved in cancer care, including specialty care providers (n=16) and primary care providers (n=6). The interview guide was based upon the Consolidated Framework for Implementation Research (CFIR). The current analysis focused solely on the “tension for change” domain. Two researchers analyzed individual transcripts using a combined thematic approach (inductive and deductive) to identify common themes and important findings. Results: While multiple barriers were identified, care coordination/communication among different specialties emerged as a notable challenge. Providers indicated that a lack of well-defined responsibilities between various specialties led to challenges in providing proper follow-up care. Most providers had not routinely utilized SCPs in their practice. Several specialty care providers expressed uncertainty about who handles follow-up care (n=11; 68.7%) while others believed that PCPs or nurses should bear that responsibility (n=5; 31.2%). In contrast, many PCPs voiced that follow-up care responsibility should fall to oncologists (n= 5, 83.3%) due to provider burden and lack of familiarity with cancer symptomatology. As a result, providers noted that patients are not receiving adequate information about their care and are unaware of their treatment needs. Specialty care providers expressed concerns that areas of non-cancer symptom management and preventive care are not being adequately addressed alongside cancer-specific symptoms. Primary care providers echoed similar concerns and noted that care tools, like SCP-PHRs and warm hand-offs, could be implemented to address these concerns. Conclusions: Barriers surrounding survivorship care coordination underscore the need for creating a efficient SCP-PHRs, as providers seek support in providing care information to patients. Providers suggested a virtual platform should be structured in a concise format that delivers comprehensive information tailored to individual needs and addresses symptoms across all stages of their cancer continuum. Future studies may focus on understanding differences in perspectives among those who have actively engaged with SCPs in their care practices.
Feasibility of using simple diet self-assessment tool (SDSAT) to establish trajectory of dietary intake for patients undergoing chemotherapy.
Authors: Cong Ming-Hua
Published: July 2024

e13805

Background: Chemotherapy is often accompanied by impaired dietary intake, which is associated with poor clinical outcomes without effective intervention. Predicting dietary changes during chemotherapy enables early nutritional support, but the dynamic pattern and interindividual variability in dietary intake during chemotherapy remain unclear. Our aim was thus to assess the feasibility of using the Simple Diet Self-Assessment Tool (SDSAT) to establish dietary intake trajectories in patients receiving chemotherapy. Methods: This study used data from an ongoing, prospective cohort study (Patient-Reported Outcome Management Including Surveillance and Intervention in Nutritional Group) of patients receiving chemotherapy in 2021 and 2022. Diet was assessed using the SDSAT once before the treatment and at least three times during one chemotherapy cycle. We applied a group-based trajectory model to identify trajectories of dietary intake. The 24-hour dietary recall (24HR) was used to verify the validity of energy and protein intake estimated by SDSAT; compliance with SDSAT was also assessed. Results: Five trajectory groups were identified for food intake based on 217 entries by 56 patients. The compliance rate accounted for 81.11% for ≥4 cumulative responses per cycle. The agreement between the SDSAT score and the dietary energy and protein intake estimated from 24HR was high (κ: 0.888–1.0, P<0.001). Groups 1 and 2 had significantly lower dietary energy/protein intake than Groups 4 and 5 (P<0.001) but with distinct dietary patterns. Group 4 was the most common dietary trajectory (35.10%). Furthermore, Groups 1, 2, and 3 had significantly weaker handgrip strength (OR: 1.12, 95% CI: 1.02–1.22, P=0.016) compared with Groups 4 and 5. Conclusions: SDSAT was feasible to establish dietary trajectories during one chemotherapy cycle. Longitudinal analysis highlights the interindividual differences in dietary intake patterns among patients receiving chemotherapy and may help to inform proactive and individually tailored nutritional interventions.
Rural palliative care in cancer: Using telemedicine to bridge the gap.
Authors: Noreika Danielle
Published: July 2024

e13807

Background: Despite the rapid growth in palliative care (PC) services, many rural regions remain without access to specialty palliative care. Community-based telemedicine may offer solutions to underserved populations from rural areas within the United States. Methods: This is a retrospective review of the creation of 2 separate rural clinics attached to the VCU Massey Comprehensive Cancer Center at CMH in South Hill, VA in 2018 (with interruption related to the Covid-19 pandemic) and in Tappahannock, VA in 2021. In addition to operational descriptions a chart review was conducted of all encounters for these clinics. Care provided was coordinated by the University PC service and the oncology clinics, including nurses and oncologists. Regulatory, legal, Information Technology (IT), and systems logistics were developed in partnership for 6-9 months prior to each pilot. There were over 100 encounters from the two periods of care for CMH (2018 until paused for pandemic towards the end of 2020; and March of 2021 to current) and greater than 50 at Tappahannock. All visits were conducted in the rural oncology clinics with assistance of oncology nursing during the encounter. Results: The average patient age was 57, and over 90% had solid tumors. On average, patients had 1-2 telemedicine visits. The most common reason for referral was symptom management, predominantly pain. Edmonton Symptom Assessment scales were collected at all visits by oncology nursing. Physical exams were completed with electronic stethoscopes and supported by oncology nursing. Medications were prescribed to rural pharmacies electronically directly by the PC physician; for the periods of clinic over the course of the Covid-19 public health emergency this included prescriptions for controlled substances (almost exclusively long and short acting opioids). For patients requiring advance care planning documents were completed electronically or by trained interdisciplinary team members in clinic in partnership with the PC physician. Technological issues occurred rarely (less than 1% of visits) and resolved without IT involvement. Conclusions: Our pilot program integrated specialist palliative care into two rural oncology clinics providing supportive care, including symptom management and goals of care discussions. Further research should define optimal integration of PC telemedicine into rural oncology.
Impact of the integration of remote clinical oncology pharmacists into routine precision medicine workflows on biomarker testing rates within The US Oncology Network community-based practices.
Authors: Greisl Natalie , Hale Brittney , Carroll Melissa , Cho Judy , Conkling Hilary , Farag Caroline , Jovani Juna , Keisler Meredith , Kendzierski Daniel , Roman Andrea , Howell Josh , Hough Shannon , Koselke Beth
Published: July 2024

e13813

Background: The US Oncology Network implemented a centralized, remote clinical oncology pharmacist review program (ClinReview) into select community-based practices. Initially, pharmacists were integrated into a precision medicine workflow process to increase biomarker testing rates among patients receiving adjuvant treatment for non-small cell lung cancer, with recommendations achieving a 100% acceptance rate. Following this success, metastatic prostate cancer patients were incorporated into the established workflow, following updated guideline recommendations for both germline and somatic testing and the 2023 approvals of PARP inhibitors in the first-line treatment setting. With previously reported testing rates only reaching 60%, we sought to evaluate the impact of the pharmacist integration into the precision medicine workflow on biomarker testing in metastatic prostate patients. Methods: Over a 4-month period, ClinReview remotely identified patients with metastatic prostate cancer during normal order review. The EMR was reviewed to assess germline and somatic testing status. If testing was not ordered, the pharmacist sent a recommendation to the treating provider. Initial testing rates for germline and somatic testing, BRCA+ status and provider acceptance rates for testing recommendations were collected. Additional data was collected utilizing a de-identified database. While additional data collection is ongoing, descriptive statistics were utilized to analyze data and the impact of the pharmacists’ interventions. Results: Across 9 practices, 142 patients were initiated on treatment for metastatic prostate cancer. At the time of initial assessment, germline and somatic testing was not ordered in 50% and 37% of patients, respectively. Pharmacists recommended additional testing in 61 patients (43%) with a 73% provider acceptance rate. Findings showed equitable testing rates across racial demographics. Pharmacist workflow integration enhanced combined germline and somatic testing rates, demonstrating an improvement from a baseline of 57% up to 77% currently. Conclusions: Community oncology practices seek to provide high-value care, including offering the most current evidence-based precision medicine testing. These findings highlight the continued need for improved somatic and germline testing in metastatic prostate cancer. However, the implemented precision medicine pharmacist workflow demonstrates the positive impact a clinical pharmacist can have on both testing rates and the potential to improve therapeutic offerings within this growing treatment space. [Table: see text]
Breaking barriers: Real-world data on immunotherapy in non-small cell lung cancer with large brain metastases.
Authors: Sadagopan Narayanan , Komlodi-Pasztor Edina , Veytsman Irina
Published: July 2024

e14002

Background: Non-small cell lung cancer (NSCLC) patients with large brain metastases (BrM) defined as > 2 cm historically face grim prognoses. Immunotherapy, emerging as a state-of-the-art treatment in NSCLC treatment, has not been extensively studied in the context of large BrM. The use of immunotherapy in these patients is complicated by factors such as steroids use and local interventions like surgery and/or radiation treatment. Methods: We conducted a retrospective study across three MedStar Georgetown Cancer Network sites to evaluate outcomes in NSCLC patients with large BrM. Inclusion criteria comprised of patients aged 18 years or older with NSCLC diagnosed between 01/01/17 to 12/31/2022 who started immunotherapy after the diagnosis of at least one BrM 2 cm or more in diameter. Intracranial progression free survival (PFS), overall survival (OS), and relevant clinical factors were analyzed. Steroid use was not included due to documentation limitations. Cox penalized regression was used to assess PFS and OS while power analysis was not done due to the sample size. Results: The study included 36 patients all of whom underwent neurosurgery and/or radiation before starting immunotherapy. Median follow up duration was 17.6 months. The population was 58.3% female, median age 64.4 years, 77.8% lung adenocarcinoma, 91.7% received pembrolizumab for immunotherapy, and median duration of immunotherapy was 178 days. Median intracranial PFS was 9.2 months and median OS reached 31 months. The hazard ratio (HR) was 0.07 (95% confidence interval (CI) 0.02-0.26) for intracranial PFS in patients who received at least 90 days of immunotherapy compared to those who received less than 90 days of immunotherapy. Each additional 30 days of immunotherapy was associated with an OS HR 0.77 (95% CI 0.67-0.90). Higher PD-L1 status was not associated with improved outcomes. Conclusions: The study highlights the potential of immunotherapy as a valuable treatment for NSCLC patients with large BrM, a population often excluded from clinical trials. In our retrospective analysis, extended immunotherapy demonstrated positive impacts on both intracranial PFS and OS. Future directions should focus on prospective evaluation of the optimal timing of immunotherapy relative to upfront large BrM treatment, with a specific emphasis on understanding the role of steroids dosing in this context.
A meta-analysis analyzing the efficacy of trastuzumab-deruxtecan (T-DXd) on central nervous system (CNS) disease in patients with metastatic breast cancer (mBC).
Authors: Ashok Kumar Prashanth , Sandhu Michael , Sravanthi Metlapalli Venkata , Desai Devashish , Suresh Kumar Vishnu Charan , Benjamin Sam
Published: July 2024

e14012

Background: CNS metastasis from mBC portends a poor prognosis. We sought to analyze CNS activity of T-DXd through a meta-analysis. Methods: A systematic search with terms encompassing BC and T-DXd was conducted in PubMed, Embase, Scopus, and Cochrane on November 23 2023. There were no search restrictions. A total of 2318 records were identified, and duplicates were removed using Mendeley. 1189 records that remained were imported into Rayyan, and the titles were screened independently by 2 reviewers. 47/75 full texts were relevant, of which 12 [7 clinical trials and 5 retrospective study] were included for analysis. Only studies that provided stratified CNS response data for mBC were included. RevMan was used to analyze the Risk Ratio (RR) and Odds Ratio (OR) with 95% Confidence Interval (CI), derived from Random Effects (RE) model with Mantel-Haenszel (MH) method. Binary RE Pooled Proportions (PP) using DerSimonian-Laird method were determined using OpenMeta. Visual inspection of our funnel plots revealed no bias. Results: The T-DXd cohort had a total of 377 patients with a median age of 54.2 years (42.5-69). Control group (T-DM1-1, Chemotherapy-2 studies) had 86 patients with a median age of 54.5 years (54.2-54.7). All studies had previously treated patients and most of the patients received local therapy. PP with T-DXd for CNS Complete Response (CR) was 4.8% (2-7.6%). Partial Response (PR) was 50.1% (32.4-67.7%) and Stable Disease (SD) was 28.9 (20.5-37.3%). PP of Objective Response Rate (ORR) (CR+PR) was 60.9% (48.3-73.5%). Drug discontinuation rate was 18% (12.2-23.9%) and pneumonitis rate was 14.5% (9.4-19.6%). RR for Event/Progressive Disease (PD) comparing T-DXd and control group was not significant [0.96 (0.77,1.2) p=0.74, I²=0%], nor was OR for Disease Control Rate (DCR) (CR+PR+SD) [1.11 (0.63,1.96) p=0.64, I²=0%] (Table). The median Progression Free Survival (PFS) was 14.1 (8.5-18.1) months for the T-DXd and 4.3 (3-5.6) months for the control group. Conclusions: Although direct comparison between the pooled T-DXd and control group failed to reveal a difference, the pooled ORR from 10/12 studies was clinically significant at 60.9%. The median PFS for T-DXd was also longer. T-DXd could be a viable treatment option for pretreated HER2+ and low mBC with CNS metastasis. Limitation of our study is the heterogeneity between the studies, entailing the need for future clinical trials in this setting. [Table: see text]
Diagnosis and genetic characterization of CNS metastases in lung cancer via shallow whole-genome sequencing of CSF cell-free DNA.
Authors: Li Yubin , Shi Zongkun , Cao Beihe , An Juan , Ding Xiaosheng , Xu Weiran , Cao Dandan , Li Xiaoyan
Published: July 2024

e14013

Background: The genetic characterization of CNS metastases in lung cancer is hindered by the limited sampling opportunities and genetic heterogeneity between intracranial and extracranial lesions. To address these challenges, this study uses cerebrospinal fluid (CSF) and blood samples, to detect and characterize CNS metastasis variants through shallow whole-genome sequencing (sWGS). Methods: From Dec. 2021 to Aug. 2023, 57 lung cancer patients were recruited, comprising 29 with leptomeningeal metastases (LMs) and 28 with only parenchymal brain metastases (PMs). A total of 66 blood and 112 CSF samples were collected for cfDNA sWGS to analyze chromosomal arm CNVs, focal amplifications (CN > 5) and SNV/InDels. Cytology was also conducted on 95 of these CSF samples. Variant differences between PMs and extracranial metastases (EMs) were analyzed using the MSK-MET database. Results: CSF cfDNA concentration was significantly lower than that in plasma (p < 0.0001), with 41.7% of samples unquantifiable, yet all samples successfully completed sWGS. The cfDNA tumor fraction in CSF was significantly higher than in paired plasma (p < 0.0001), and most arm CNVs and gene amplifications exclusively detected in CSF. Cytology, as the gold standard for LM diagnosis, had a sensitivity of 0.76. The sensitivity for LM diagnosis based on aneuploidy and genomic amplification fraction (GAF) were 0.51 and 0.80, respectively, without compromising specificity. Gains in 1p, 7p, 11q, 16p, and 17q, as well as losses in 9p and 9q, were significantly more frequent in PMs compared to EMs and further increased in the LMs (p < 0.05). Notably, losses in 1p, 4p, 5q, and 11p, significantly more frequent in PMs than in extracranial metastases, but showed a significant increase in gain frequency in LMs (p < 0.05). In the LM group, the frequency of EGFR L858R and amplification of nearly the entire 7p where the EGFR located, were significantly increased, whereas KRAS G12D frequency significantly decreased (p < 0.05). Conclusions: The characteristics of extremely low concentration but high tumor fraction of CSF cfDNA make it suitable for sWGS, enhancing LM diagnostic sensitivity without compromising specificity, and identifying molecular characteristics of CNS metastasis. These molecular features require further validation in larger prospective clinical cohorts, offering potential for personalized diagnosis and treatment of CNS metastases.
Prognostic factors of grade 4 IDH-mutant astrocytoma.
Authors: Maqbool Muhammad Asad , Jenkins Robert B. , Ida Cristiane M. , Burns Terry C. , Kizilbash Sani Haider
Published: July 2024

e14019

Background: The data on the prognostic factors of grade 4 IDH-mutant astrocytoma remains limited since the 2021 update of the WHO classification of Central Nervous System tumors. This update recognizes the importance of molecular characteristics and confers a grade 4 diagnosis based on the presence of at least one of either necrosis, microvascular proliferation, or CDKN2A/B homozygous deletion. This study sought to determine the factors that impact prognosis of patients with grade 4 IDH-mutant astrocytoma. Methods: A retrospective review was performed on all patients diagnosed with grade 4 IDH-mutant astrocytoma on initial diagnosis (as defined by the 2021 WHO classification) across the three Mayo clinic campuses (Minnesota, Florida, Arizona) between 2002 and 2023. Datapoints collected included demographic, clinical, imaging, histological and molecular variables. Factors impacting survival outcomes (overall survival [OS] and progression free survival [PFS]) were evaluated using Cox regression models. Results: Sixty-two patients with grade 4 IDH-mutant astrocytoma were identified (43 based on histological criteria alone, 10 based on molecular criteria alone, and 9 based on both). The median age of the patients was 36 years, with 64.5% of the patients identified as male and 93.3% as white. 100% (n=58) of these patients received standard treatment after surgery (radiation/temozolomide). The median follow up was 3.3 years. The median PFS and OS were 3.2 and 6.9 years, respectively. The OS was impacted by an unfavorable tumor location (either tumor involving the midline or at least 3 brain lobes; 2.4 years vs. 12.8 years, HR 10.8 [95% CI 3.29-35.6], p<0.001) and CDKN2A/B homozygous deletion (2.5 years vs. NR, HR=4.3 [95% CI 1.5-12.3], p=0.0065). The PFS was impacted by an unfavorable tumor location (1.4 years vs. 4.6 years, HR=5.3 [95% CI 2.21-12.7], p=0.002), CDKN2A/B homozygous deletion (1.4 years vs. 4.6 years, HR=6.2 [95% CI 2.71-14.2], p<0.001) and MGMT promoter hypermethylation (4.6 years vs. 1.4 years, HR=0.369 [95% CI 0.154-0.883], p=0.025). Age, sex, tumor size and the use of tumor-treating fields did not significantly affect survival outcomes. Using multivariable analyses, PFS remained significantly impacted by CDKN2A/B homozygous deletion (HR=11.3 [95% CI 3.23-39.0], p=0.0001) and MGMT promoter hypermethylation (HR=0.243 [95% CI 0.082-0.717], p=0.0104), but not by an unfavorable tumor location (p=0.819). Conclusions: Both CDKN2A/B homozygous deletion and MGMT status may independently influence the progression-free survival of patients with grade 4 IDH-mutant astrocytoma.
Convolutional neural network and glioma genotyping: A systematic review.
Authors: Ashayeri Hamidreza , Abdollahi Mirsaeed , Jafarizadeh Ali , Morsali Soroush , Pedrammehr Siamak , Alizadehsani Roohallah , Gorriz Saez Juan Manuel
Published: July 2024

e14038

Background: Gliomas are the most common primary intracranial tumors. Overall, there are 23 different glioma types, and the grading and prognosis of each type are determined by their specific mutations. Several identified mutations are IDH gene status, CDKN2A/B homozygote delegation, PTEN mutation, p53 mutation, TERT promotor mutation, H3K27M mutation, MGMT promotor methylation, trisomy 7/monozomy10, EGFR amplification, ATRX mutation, 1p/19q codeletion, and BRAF mutation. These specific mutations and genomic features can have their distinctive radiologic features seen in different magnetic resonance imaging (MRI) sequences. By using a Convolutional Neural Network (CNN) for feature extraction, the genotyping power of MRI for glioma could be increased. To address this, we systematically reviewed the use of different CNN-based models to detect the genetic context of glioma based on the MRI images. Methods: We conducted a systematic search in PubMed, Embase, Scopus, Web of Science, and Google Scholar. We included original peer-reviewed human studies (retrospective or prospective), focusing on the use of CNN in individuals with glioma. We excluded animal studies, studies with no CNN-based models, reviews, book chapters, conference abstracts, and case reports. JBI checklists were utilized for quality assessment. Results: The initial search resulted in 973 articles. after removing duplicates, 563 studies entered the screening process by title and abstract. 59 studies met our inclusion criteria (56 retrospective and 3 prospective cohort studies) with a total of 26434 glioma patients included (studies ranged from 21 – 2648 individuals). 31 studies used CNN methods only in different stages of image processing (tumor segmentation, feature extraction, image encoder) and 28 studies used CNN as a classifier and mutation predictor. ResNet was the most commonly used CNN-based model (n = 14). U-net (n = 7) and DenseNet models (n = 4) were other commonly used CNN-based models. Included studies targeted IDH status (n=44), 1p/19q codeletion (n=18), MGMT promotor methylation (n=11), ATRX mutation (n=5), TERT promotor mutation (n=5), CDKN2A/B homozygote deletion (n=3), PTEN mutation (n=3), p53 mutation (n=3), H3K27M mutation (n=2), trisomy 7/monozomy10 (n=2), EGFR amplification (n=2), and BRAF mutation (n=1). Highly severe methodological heterogeneity among these studies excluded the possibility of meta-analysis. Conclusions: Current studies have shown that, as a non-invasive method, using CNN-based models on multiple MRI sequences increases the power of early detection and prediction of glioma genetic types before pathological confirmation and has promising results. However, DL performance varies among mutations. Combining multiple DL models with clinical and radiomic features in different and larger databases can further increase the final results.
Incidence of venous thromboembolism in newly diagnosed glioblastoma multiforme and associated risk factors: A retrospective chart review.
Authors: Al Majarafi Nasser , Binjabal Duaa Omar , Pond Gregory Russell , Hirte Hal W.
Published: July 2024

e14040

Background: Patients diagnosed with glioblastoma multiforme (GBM) are recognized as a population at high risk of developing venous thromboembolism (VTE) (1,2). A retrospective chart review of patients diagnosed with GBM at the Juravinski Cancer Centre (JCC) was performed with the primary objective to assess the incidence of the development of VTE in newly diagnosed GBM. The secondary objective was to identify patients who were at higher risk and who could benefit from prophylactic anticoagulation. Methods: This was a single-centre, retrospective cohort study. We reviewed the charts of 528 patients diagnosed with GBM at the JCC from an 8-year period from January 1, 2013 to December 31, 2020. Information on the following factors was collected: Body-mass index (BMI), comorbidities (hypertension, diabetes, dyslipidemia, smoking history), performance status, location and size of tumour, degree of resection, presence of and location of weakness, baseline blood counts, treatments administered, date of diagnosis and time to death or last follow-up. Results: Over the period of review, a total of 528 patients were identified. 111 patients (21%) were diagnosed with VTE. The location of VTE was as follows: 39 patients (35%) unilateral lower extremity deep venous thrombosis (DVT), 8 (7%) unilateral upper extremity DVT, 8 (7%) bilateral lower extremity DVT, 30 (27%) pulmonary embolism (PE), and 25 (23%) DVT and PE. Most VTE (87%) occurred within 12 months of diagnosis of GBM. On univariate and multivariate analysis, no factors were identified that contributed to an increased risk of VTE. Conclusions: Newly diagnosed patients with GBM have been shown to have a significant risk of developing VTE. The AVERT study (3) demonstrated the preventive benefit of administering a direct oral anticoagulant (DOAC) to cancer patients, including those with GBM, at high risk of developing VTE (3). Thus consideration should be given to treating patients with GBM with a DOAC at the time of diagnosis. The benefit of preventive treatment will need to be balanced against the risk of bleeding in these patients. References: 1. Marras LC et al. Cancer 2000; 89(3):640–6; 2. Lim G et al. Cureus 2018;10(5): e2678; 3. Carrier M et al. N Engl J Med 2019; 380:711-9.
Pineal gland: Sleep, malignancy and statistics.
Authors: Pereira Kristal , Ali Hassan , Thirumaran Rajesh , Desai Krishna
Published: July 2024

e14042

Background: The pineal gland is a neuroendocrine gland located deep in the middle brain that regulates the circadian rhythm through Melatonin. Pineal parenchymal tumors arise from pineocytes, have no sexual predominance, occur most frequently in the pediatric population and result in melatonin level disruptions.Pineal region tumors can spread via CSF to other areas in the CNS. The first treatment for pineal region tumors is surgery. Treatments after surgery may include radiation, chemotherapy or clinical trials. Methods: Data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). Pineal gland tumor cases that were labeled as the primary site were extracted from the data base. Further selection was made using the ICD Code D75.3 for neoplasm of pineal gland-primary site labelled. The data was stratified based on age, sex, race and survival curves were compared using the Log-Rank test (GraphPad Prism). Results: A total of 416 pineal gland tumor cases were found, of which ~ 50.48% were males. These tumors were most commonly seen in White (51.68%) patients followed by Hispanic (23.32%), Black (16.10%), Asians/Pacific Islander (6.97%) and Alaskans/Native American (0.96%) patients. The median age of diagnosis was 24.5 years. The incidence rate (per 1,000,000 population) for the general population has increased from 0.69 in 2000 to 0.73 in 2020. As of 2020, the incidence was noted to be higher in males, although overall the incidence among females has been ion the rise. Incidence rate was highest among the Native Americans/Alaskans population followed by Hispanics, Asians/Pacific Islanders, Blacks and Whites. Within the races, incidence was noted to be increasing in the Native Americans/Alaskans & Hispanic populations, stable in the Asians/Pacific Islanders & Black populations and decreasing amongst the White population over the period of 20 years. When the survival curves were compared on the basis of gender and race, the data was clinically significant only for gender. The median of survival (mOS) for males was 146 months but was undefined for females (CI:5.344-12.55, HR: 8.191, p <0.0001) mostly likely due to zero death events being recorded for females. Conclusions: Pineal gland tumors are rarely encountered malignancy with only 416 case reported in the last two decades. It has an almost equal predilection for males and females, more common in the younger population. The incidence is higher among males, although being relatively constant since 2000, and is trending up in females. Overall survival was superior in females with no reported death events. Native Americans/Alaskans are more affected overall survival is independent of the race.
Analysis of effectiveness of FLOT perioperative chemotherapy in resectable locally advanced gastric or esophago-gastric junction cancer in a Kazakhstani population.
Authors: Kerimkulov Altay , Sarina Tomiris , Uskenbayev Talgat , Usipbekov Bayduysen , Umerzakova Bakhtzhan , Kovalchuk Dina , Sipenova Aigerim
Published: July 2024

e16129

Background: Gastric cancer is the third most common malignancy in Kazakhstan and the second leading cause of cancer-related mortality. Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) perioperative chemotherapy is widely accepted treatment strategy of locally advanced gastric adenocarcinoma in Western countries. However, radical surgery is a preferable approach in Kazakhstan. The objective of this study was to assess the effectiveness and feasibility of FLOT perioperative chemotherapy in curable locally advanced gastric or esophago-gastric junction cancer. Methods: In this study, we reviewed the retrospective data of patients with locally advanced gastric or esophago-gastric junction cancer, who received FLOT perioperative chemotherapy between January 2020 and December 2022 in single center. To evaluate the effectiveness of treatment, histopathological regression, disease free survival (DFS) and 1- and 3-year overall survival outcomes were analyzed. Results: Total 136 patients with stage II and III with gastric or esophago-gastric junction cancer were treated. Fifty-six patients (41%) received FLOT preoperative chemotherapy. 9% (5) patients couldn’t complete all cycles of chemotherapy due to serious adverse events. Disease progression was observed in 10 (19%) patients after FLOT preoperative chemotherapy. Of the 46 radically operated patients, 5 (11%) had complete or near complete pathology response, 33 (72%) patients had partial response, and 8 (17%) patients had no response for preoperative chemotherapy (p = 0,405). 7 patients had not get adjuvant chemotherapy. Overall, 1- and 3-year survival were 78,6% and 34,9% respectively, disease free survival was 76,8% and 39% respectively. Conclusions: The FLOT perioperative chemotherapy was effective and feasible to administer and might be a standard treatment option among patients with locally advanced gastric or esophago-gastric junction cancer.
Potential impact of malnutrition on patients with hepatocellular carcinoma undergoing liver transplantation: A nationwide analysis.
Authors: Obeidat Adham , Mansour Nour , Mahfouz Ratib , Aldiabat Mohammad
Published: July 2024

e16233

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer mortality worldwide. Liver transplantation is the ideal treatment for HCC, and the Milan criteria, which has been the international gold standard, provided the opportunity for HCC patients to undergo liver transplantation with favorable outcomes. On the other hand, malnutrition is a prevalent condition, and carries a substantial burden on health and social-care systems. In this study, we aim to look at the potential impact of malnutrition on in-hospital mortality and other outcomes in HCC patients undergoing liver transplantation. Methods: The United States Nationwide Inpatient Sample (NIS) was used to extract hospitalization data of patients admitted between 2016 to 2018. Using ICD10 revision codes, we identified adults with a diagnosis of HCC, with or without cirrhosis, who underwent liver transplantation with concomitant malnutrition. The control group included HCC patients without malnutrition. The primary outcome was the in-hospital mortality. Secondary outcomes included length of stay (LOS), acute kidney injury (AKI) and hyponatremia. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 33,321 patients were admitted with HCC during the study period. 503 of them underwent liver transplantation, and of those, 75 patients had the diagnosis of malnutrition. In this group of patients, the mean age was 60.3 years. 30% were females and 60% were Caucasians. When adjusted to other relevant variables, malnutrition was associated with increased in-hospital mortality (OR 2.42; P-value 0.033). It was also associated with increased chance of developing an AKI (OR 1.95; P-value 0.014). Moreover, it was associated with increased LOS (OR 1.18) and increased chance of liver transplant rejection (OR 1.47), however, these were not statistically significant. Other factors associated with increased in-hospital mortality in HCC patients undergoing liver transplantation are described in the table. Conclusions: Malnutrition is a potentially treatable condition, however, when untreated it may contribute to poor health and economic outcomes. In this study, HCC patients with malnutrition who underwent liver transplantation, have an increased chance of in-hospital mortality. Furthermore, they had an increased odds of developing an AKI which in turn can prolong the hospital length of stay and total charges. We recommend that clinicians pay more attention to identify patients with or at increased risk for malnutrition in order to treat and optimize them prior to liver transplantation, and therefore to prevent such complications. [Table: see text]
Treatment duration of adjuvant immune checkpoint inhibitor in hepatocellular carcinoma after curative resection: A prospective cohort study.
Authors: Pan Li-Xin , Su Jia-Yong , Li Le , Fan Xiao-Hui , Ma Liang , Zhong Jian-Hong
Published: July 2024

e16266

Background: Adjuvant immune checkpoint inhibitors (ICIs) improve the recurrence-free survival for patients with hepatocellular carcinoma (HCC) after hepatic resection. However, the appropriateness of the treatment duration is unknown. This prospective cohort study aims to evaluate the effect of adjuvant ICIs duration in patients with HCC at high risk of recurrence after curative hepatic resection. Methods: Recurrence-free survival, overall survival, and adverse events were compared in patients receiving adjuvant ICIs therapy for more than 6 months or up to 6 months between March 2019 and March 2023. Patients who with HCC recurrence within 6 months after hepatic resection were excluded. Results: Of the 118 patients, 53 (44.9%) received longer than 6 months of adjuvant therapy, 65 (55.1%) received up to 6 months of adjuvant therapy. Recurrence-free and overall survivalwere significantly longer among patients who received longer than 6 months of adjuvant therapy than among those who received up to 6 months adjuvant therapy (HR 0.47, 95%CI 0.24–0.92, P = 0.021; HR 0.28, 95%CI 0.08–0.93, P = 0.045). However, patients who received more than 6 months of adjuvant therapy had a higher rate of adverse events than those who received up to 6 months of adjuvant therapy, especially grade 2 adverse events. Conclusions: Six months of adjuvant ICIs therapy may not be enough, but prolonged adjuvant therapy can significantly increase the incidence of adverse events. This study highlights the need to optimize the duration of adjuvant ICIs after curative resection for HCC in order to minimize risk of not only recurrence but also adverse events.
Neoadjuvant immune-checkpoint blockade therapy combined with TACE for resectable hepatocellular carcinoma with high recurrence risk: A phase II, single-arm clinical trial (MORNING).
Authors: Tan Li , Xu Lixia , Shen Shun-Li , Li Dongming , Hua Yunpeng , Li Shaoqiang , Liang Lijian , He Qiang , Zhou Qi , Xie Wenxuan , Chen Zebin , Wu Jian , Li Jiaping , Fan Wenzhe , Zhuang Wenquan , Chen Lili , Feng Shiting , Peng Sui , Wang Jiping , Kuang Ming
Published: July 2024

e16267

Background: Prognoses of patients with hepatocellular carcinoma (HCC) remain unsatisfactory due to the high recurrence rate after curative hepatectomy. In this study, we investigated the safety and efficacy of neoadjuvant Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) in combination with transarterial chemoembolization(TACE) for patients with high recurrence risk. Methods: For this phase II, single-centre, single-arm trial, resectable HCC (BCLC stage A/B) participants were enrolled, who should meet at least one of the following high-risk criteria: a) Multiple tumors or satellite lesions (≥2); b) tumor diameter>5cm (single tumor); c) AFP ≥ 400 ug/L; d) Predicted to be positive by the Microvascular invasion prediction model of our center according to preoperative imaging. All of the patients received two cycles of Cadonilimab(10mg/kg, Q3W) after TACE treatment. After resection, patients received additional 12 months of Cadonilimab(10mg/kg, Q3W) in the adjuvant setting. The primary end-point was the major pathologic response (MPR, defined as >90% necrosis of the resected tumour), the secondary endpoints are objective response rate (ORR), one-year recurrence rate and safety. Results: Between Apr 26th, 2023, and Jan 5th, 2024, 19 patients were enrolled, 84.2% of whom were male, with the mean age of 55. 9(47.4%) patients had more than one tumor and 13(68.4%) patients had tumors larger than 5cm. All patients received neoadjuvant TACE and at least one cycle of Cadonilimab. Of the 15 patients underwent successful resection, 7(46.7%) had MPR, while 12(80%) of them had 70% or greater tumour necrosis. 11 patients had partial response and the ORR was 73.3% per mRECIST. Additionally, only one patient received a partial response, while twelve patients maintained stable decease as assessed by RECIST1.1. 19(100%) patients had treatment-related adverse events of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were ALT/AST increase (94.7%), abdominal pain (73.7%) and bilirubin increase (57.9%). 4 patients had grade 3 adverse events, including infusion reaction (2 patients), white blood cell decreased (2 patients) and fever (1 patients). The abdominal pain and fever were more relevant to TACE. No grade 4 or 5 events were observed. Conclusions: Cadonilimab combined with TACE as a neoadjuvant therapy seems to demonstrate safety and promising efficacy. Clinical trial information: NCT05578430 . [Table: see text]