bluuebunny/crossref_metadata_2025 huggingface dataset:
Will COVID-19 directives to reduce regularly scheduled physical examinations affect recurrence detection in patients with early breast cancer?
Authors: Beltran-Bless Ana-Alicia , Alshamsan Bader , Alzahrani Mashari J. , Hilton John Frederick , Samuel Vicky , Baines Kelly-Anne , Pond Gregory Russell , Vandermeer Lisa , Clemons Mark J. , Larocque Gail
Published: June 2022

1532

Background: The COVID-19 pandemic has significantly reduced routinely scheduled in person assessment and examination of early breast cancer patients (EBC). To assess if this is likely to impact the detection of recurrent disease, we reviewed recurrence patterns of EBC patients enrolled in a survivorship program that adheres to ASCO guidelines. Methods: Charts of EBC patients transferred through a single center Wellness Beyond Cancer Program (WBCP) and who subsequently had a breast cancer recurrence between February 1, 2013 and January 1, 2019 were reviewed. Patient, tumor and treatment characteristics were evaluated. Results: Of 206 patients eligible for the current study, 41 patients had ipsilateral breast recurrences (19.9%), 135 had distant recurrences (65.5%) and 30 had contralateral new breast cancers (14.6%). Ipsilateral breast recurrences were detected by the patient in 53.7% (22/41) and by routine imaging in 41.5% (17/21). The majority of distant recurrences (125/135, 92.6%) were detected via patient-reported symptoms. Contralateral breast primaries were detected by patients 16.7% (5/30) or by routine imaging (83.3%, 25/30). Only 2/206 (1.14%) recurrences/new primaries were detected by healthcare providers at routinely scheduled follow-up visits. There was a statistical difference in recurrence detection between image detected vs. self-detected in the following factors: grade 3 (26.5% vs 51%, p < 0.007), triple negative breast cancer (3.9% vs. 15.1%, p = 0.03), HER2 disease (18.4% vs. 9.8%, p = 0.04). Conclusions: Despite following ASCO follow-up guidelines for routinely scheduled follow-up appointments with physical examination, healthcare providers rarely detect recurrence disease. While reduced in person visits may affect other aspects of follow-up (e.g., toxicity management), it appears unlikely, provided patients attend regular screening tests, that reduced in-person follow-up is associated with worse breast cancer-related outcomes during the COVID-19 pandemic. [Table: see text]
CONTINUUM: A pilot care transition intervention for hospitalized patients with advanced cancer.
Authors: Lage Daniel E , Schmelkin Alane , Cohn Julia , Miller Laurie , Kuhlman Caroline , Krueger Elizabeth A. , Olivier Kara Marie , Haggett Dana , Ritchie Christine , Greer Joseph A. , El-Jawahri Areej , Nipp Ryan David , Temel Jennifer S.
Published: June 2022

1534

Background: Patients with advanced cancer are frequently hospitalized and experience burdensome transitions of care after discharge. Interventions to address patients’ symptoms, support medication management, and ensure continuity of care after discharge are lacking. We sought to demonstrate the feasibility and acceptability of CONTINUUM (CONTINUity of care Under Management by video visits) for this population. Methods: We conducted a single-arm pilot trial (n = 54) of CONTINUUM at Massachusetts General Hospital (MGH). The intervention consisted of a video visit with an oncology nurse practitioner (NP) within 3 business days of hospital discharge to address symptoms, medication management, hospitalization-related issues, and care coordination. Prior to discharge, we enrolled English-speaking adults with advanced breast, gastrointestinal, genitourinary, or thoracic cancers experiencing an unplanned hospitalization who were receiving ongoing oncology care at MGH and being discharged home without hospice services. We defined the intervention as feasible if ≥70% of approached and eligible patients enrolled and if ≥70% of enrolled patients completed the intervention within 3 business days of discharge. At 2 weeks after discharge, patients rated the ease of use of the video technology and stated whether they would recommend the intervention. NPs completed post-intervention surveys to assess fidelity to the intervention protocol. Results: From 01/07/21 to 05/28/21, we enrolled 54 patients (77.3% of patients approached). Of the enrolled patients (median age = 65.0 years; 59.3% and 22.2% had advanced gastrointestinal or thoracic cancers, respectively), 83.3% of enrolled patients received the intervention within 3 business days of discharge. Patient rating of the ease of use of video technology was a mean of 7.8 out of 10, with 71.4% stating they “agreed” or “strongly agreed” that they would recommend the intervention. NP post-intervention surveys revealed that visits focused on symptom management (85.7%), followed by addressing post-hospital care issues (69.0%). At 30 day follow up, 38.8% were readmitted within 30 days of discharge, and 12.2% died within 30 days of discharge. Conclusions: We found that CONTINUUM, which consists of an NP-delivered video visit soon after hospital discharge addressing patients’ symptoms, medications, and care coordination, represents a feasible and acceptable approach to provide post-discharge care for hospitalized patients with advanced cancer. Future studies will test the efficacy of the intervention for reducing hospital readmissions. Clinical trial information: NCT04640714.
Cancer health disparities in the state of Georgia: African American oncology care.
Authors: Karki Nabin Raj , Zarkua Kristina , Bano Kulsum , Chahin Michael , Keruakous Amany R.
Published: June 2022

1546

Background: Approximately 58,970 new cancer diagnoses are projected for 2022 in Georgia (GA), contributing to 18,750 deaths. African Americans (AA) make up about one-third of Georgia’s population compared to 14% of the national population. Cancer survival rates are lower for AA than non-AA for almost all cancer types. Biological factors do not account for all these differences. We explore the impact of racial disparities on cancer care in Georgia. Methods: We used 2020 behavioral risk factor surveillance system (BRFSS) data to capture patient-reported data on various demographic and health coverage variables. Oncology patients in the stage of Georgia were selected for our analysis. We evaluated the effect of racial disparities on clinical services received. Results: In the state of GA, 9,090 participants responded to the 2020-BRFSS, of which 400 partcipants had a history of cancer diagnosis other than skin cancer. Males and females comprised 37% and 63%, respectively. AA represented 15.8% of the respondents. The majority of the oncology respondents reported having health care coverage (96%) and having insurance coverage for all cancer treatments (96.8%) despite having 81.9% of the participants unemployed. Compared to non-AA, AA participants reported lower rates of health insurance payment for cancer treatment (84% v 99.3%, P = 0.0022) and lower levels of annual incomes (percentage of annual income <50,000$/year was 72.3% vs 51.5%, P = 0.0151). AA participants were four times less likely to have full coverage for cancer-related treatment than non-AA (odds ratio=4.31). There was no statistically significant difference in secondary education rates, health care coverage, the inability to see a physician due to cost, receipt of summary of treatment or written instructions, denial of insurance coverage due to cancer, and clinical trial participation. Participants with at least secondary education were more likely to have full insurance coverage for all cancer treatment expenses (P = 0.0206). Conclusions: Among cancer patients in Georgia, income rates were lower in AA than in non-AA. They were also less likely to have full coverage for cancer-related treatment. Analysis suggests secondary education increases the likelihood of having full insurance coverage. Education and income disparity may have a bearing on the accessibility and quality of cancer care. Addressing these inequities on a societal level will be key in ensuring high-quality oncology care for all. [Table: see text]
Development of an electronic health record registry to facilitate collection of Commission on Cancer (CoC) metrics for patients undergoing surgery for breast cancer.
Authors: Lyu Heather G. , Kantor Olga , Laws Alison , McDonald James , Pham Lisa , Dominici Laura Stewart , Vincuilla Julie , Raut Chandrajit P. , Danilchuk Bryan , Novak Lara , Parker Tonia , King Tari A. , Mittendorf Elizabeth A.
Published: June 2022

1549

Background: Accurate and efficient data collection is a challenge for quality improvement initiatives and clinical research. We describe the development of a custom electronic health record (EHR) based registry to automatically extract structured Commission on Cancer (CoC) axillary surgery specific metrics from a custom synoptic note template included in the operative reports for breast cancer patients undergoing surgery. Methods: The “Smart” functionality of our enterprise-based EHR system was leveraged to create a custom Smart phrase to capture axillary surgery specific variables. A multidisciplinary team developed structured data elements correlating to each axillary surgery-specific variable. These data elements were then included in a note template for the operative report. Each variable could be aggregated and converted into a single flat database through the EHR’s reporting workbench and serve as a live, prospective registry for all users within the EHR. Results: The final axillary surgery-specific note template in a synoptic format allowed for efficient and easy entry and automatic collection of breast cancer specific metrics. From initial adoption in February 2021 through December 2021, there were 1,254 patients who underwent breast surgery with axillary surgery. The operative notes allowed for automatic capture of metrics from 60.5% (n = 759) of patients. Data capture improved from 37.6% in the initial adoption period of six months to 86.2% in the last five months. Capture rate in December 2021 was 98%. Conclusions: We were able to demonstrate successful implementation of provider driven structured data entry into EHR systems that permits automatic data capture. The end result is a custom synoptic note template and a real-time, prospective registry of breast cancer-specific CoC metrics that are robust enough to use for quality improvement initiatives and clinical research.
Using machine learning on real-world data to predict metastatic status.
Authors: Green Foad H. , Huang Hu T. , Lerman Michelle , Tran Mary , Subramanian Vinod , Loving Joshua , Rioth Matthew J.
Published: June 2022

1550

Background: Real world data (RWD) is increasingly used to inform research, patient care, and population health in oncology; however, using RWD at scale requires accurate methods to identify clinically-relevant attributes. Metastatic status is a highly relevant clinical attribute in cancer patients but it is not routinely captured in structured formats and its determination conventionally requires review and interpretation by certified tumor registrars (CTRs). Clinical diagnoses, treatments, imaging procedures and other clinical variables documented in electronic health records (EHRs) can be used to differentiate metastatic from non-metastatic patients. This study describes an effective machine learning approach in utilizing prevalent and standardized data elements from EHRs across multiple health systems. Methods: 28,043 lung cancer and breast cancer patients from two large health systems within the Syapse Learning Health Network with data sources from CTR abstraction and EHRs were analyzed. Patients were labeled for reference metastatic status by CTRs and split into training (n = 22,434) and testing (n = 5,609) cohorts, with proportionate distribution of cancer type and metastatic status between cohorts. A regularized gradient boosting algorithm, XGBoost, was trained using over 750 variables from the patient records collected at the time of or after the initial cancer diagnosis. Results: Integration of ICD-10-CM codes with antineoplastic treatment history and radiologic imaging procedure orders achieved metastatic status prediction with increases to precision and recall in lung cancer (21% and 32% respectively) and breast cancer (39% and 9% respectively), when compared to the use of only ICD-10-CM diagnosis codes for secondary malignant neoplasms (Table). The addition of treatment and procedure data from different cancer types improved the model classification within individual cancer types. Conclusions: One of the biggest challenges in using RWD for precision oncology is identification of clinically-relevant phenotypes at scale. Here we demonstrate a scalable evidence-based method utilizing structured data for imputing metastatic status with high predictive power from two separate health systems. With further validation, this approach may be generalized to other cancer types, applied to temporal slices of data to identify changes in metastatic status, as well as provide a high-confidence designation of metastatic status for other use cases such as staging.[Table: see text]
Can an artificial intelligence-based platform reduce physician burden and increase access to clinical trials?
Authors: Gortzak Uzan Limor , Lichtenfeld J. Leonard Leonard , Bader Tzvia , Gaziel Avital
Published: June 2022

1552

Background: Clinical trials for cancer patients are an important treatment option and a resource for drug development. Although patients are more actively searching for treatment options through various approaches, the national average of cancer patients accrued to clinical trials remains static at only 2-4%. The most widely recognized resource is clinicaltrials.gov, which does not offer direct trial matching, is geared toward healthcare professionals and uses complex medical terms that are challenging for many patients. For clinicians, the absence of real-time access and insight into all relevant oncology trials, forms a burden on their already-limited time. Alleviating this burden could reduce barriers to clinical trial accrual. Methods: Using AI and an unsupervised natural language process approach, the Trialjectory platform monitors, analyzes and matches patients to clinical trials. Matching is achieved by patient response to a dynamic set of questions curated based on the eligibility criteria of available trials. The online questionnaire (www.trialjectory.com) collects detailed clinical data that include disease characteristics (histological, molecular and mutational status), treatment history, general health and comorbidities. All collected data points are incorporated into the matching process, yielding a high-quality actionable matched-trial list. A skilled support team is available to answer questions and concerns via email, text or phone calls. The platform enables patients to share the matched trial list with their oncologist for discussion. Results: from July 2019 - December 2021, 49,906 cancer patients completed Trialjectory’s questionnaire. Patient accrual grew rapidly since the second half of 2019 with 1462, 2201, 9364,12685, and 24194 new questionnaire completions in each consecutive 6-month period from the 2nd half of 2019 through December 2021. 49,199 (98.6%) of registered patients were found eligible for available trials. Of the matched patients, 4428 patients (9%) applied to a clinical trial. Our matching engine identifies each specific trial match to each patient profile with a sensitivity of 90% and a specificity of 95%. When aggregated to a patient level, the chance that a patient will be matched for at least one trial from those that he is eligible to is 99.9%. Metrics are validated by automatically matching multiple artificially-created patient profiles and manually verifying the quality of the match. Conclusions: TrialJectory is an effective AI-based tool that offers cancer patients and their oncologists direct, precise and quick access to relevant clinical trials. Our data show a high adoption and growing registration rates and well-above average clinical trial application rate. By democratizing the access to clinical trials, increased opportunities are noted that might lead to increased trial participation.
Applicability of a web app for breast cancer risk calculation and personalized recommendations for screening in Mexico.
Authors: Muñoz Lozano Jose Felipe , Zayas Omar A. , Salazar-Mejía Carlos Eduardo , Oyervides Victor , Vidal-Gutiérrez Oscar , Pineiro-Retif Rafael , Garza Brenda , Gomez Ricardo Andres , Renteria Larisa , Pérez-Ibave Diana Cristina
Published: June 2022

1567

Background: A minority of women with breast cancer in Mexico are being diagnosed through a screening program, which translates into late diagnosis and a worse prognosis. It is imperative to develop easy access and low-cost interventions to increase the screening rate. Methods: We developed a web app tailored to guide patients to seek medical consultation if they were at high risk for breast cancer or standard screening recommendations based on the predicted risk for age (https://cuccuanl.com/calcula-tu-riesgo-de-cancer-de-mama/). The web app consisted of an 8-question survey designed using object-based programming with HTML5, the additional logic was programmed on JavaScript. The program logic automatically guided patients to medical consultation if they were at high risk for breast cancer, or standard screening recommendations based on their predicted risk for age. On each confirmation page, the contact information of the hospital appeared, also, consultation at the clinic could be scheduled within the web app. The web app was distributed via social media on International Breast Cancer Awareness Day. Results: A total of 1,012 persons answered the survey after a follow-up period of two weeks. The median age of respondents was 34 years. Among participants, 10.8% were considered at very high risk for breast cancer due to symptoms, 22% were classified as high risk based on family history or more than 5 years of contraceptive use, and 19% were considered as average-risk population for whom age-based screening tests were recommended. The remaining 48% of participants were considered at low risk for breast cancer development and were directed to educational information about breast cancer awareness. Among all persons that answered our survey, 21 requested a specialized medical appointment within the web app. Conclusions: This pilot study showed a high response of Mexican population seeking breast cancer risk evaluation, 11% of women that responded to our survey had symptoms highly suggestive of breast cancer. The use of web apps can result in mass diffusion which will help reach people with less medical access, a common scenario in many developing countries. Further analysis should be made to measure the real impact on breast cancer diagnosis and oncological outcomes. This study shows how effective social media is as a means of diffusion on health topics. [Table: see text]
Interface software can markedly reduce time and improve accuracy for clinical trial data transfer from EMR to EDC: The results of two measure of work time studies comparing commercially available clinical data transfer software to current practice manual data transfer.
Authors: Thompson Maureen , Grenier Len , Alvarez Catarina , Poon Gary , Melear Jason M.
Published: June 2022

1573

Background: Clinical studies and new drug approvals are delayed by slow data transfer and transcription errors from site entered data. These delays have been compounded by a shortage of data entry personnel at sites such that data entry approaches 10-30 days post visit. Data transfer is largely performed by manual keyboard entry from electronic medical records (EMR) into electronic case report forms (ECRF). Methods: We conducted two separate measure-of-work time studies to compare a commercially available interface software product, ProXimity to the current manual data entry. The clinical trial data from two different EMRs (ARIA and IKM G2) to an EDC (Medidata Rave). The EDC mirrored an IRB approved clinical study. Time to transfer data and error rates were the primary and secondary endpoints, respectively. For study 1 Aria EMR data from 3 subjects and 1497 data fields including demographics, vital signs, ECOG PS, physical findings, adverse events, and lab results including CBC, CMP, urinalysis, coagulation, serology were selected for visits from Screening and C2D1. For Study 2 IKM G2 data from 6 subjects and 834 data fields included demographics, vitals, and lab results. The data entry personnel were aware of the timed nature of the study. Results: Study 1 ProXimity took 13.2 min to transfer the data compared to 73.4 min for manual entry, with error rates of 0.8% compared to 3.5%, respectively. In Study 2 Proximity took 6.5 min compared to 29 min for manual entry, with error rates of 1.4% each due to non- conformant data (text). Conclusions: Software data transfer interfaces can markedly shorten the time for data entry, reduce error rates and reduce operational costs.
Market determinants of commercial prices for intravenous chemotherapy infusions.
Authors: Milligan Michael , Orav E. John , Mitchell Aaron Philip , Lam Miranda
Published: June 2022

1585

Background: Recent price transparency legislation mandated that hospitals across the country report their individually negotiated prices with insurers. Using this data, we sought to characterize the prices paid for standard intravenous (IV) chemotherapy infusions, and determine the hospital, regional, and market factors associated with higher prices. Methods: We utilized a database of U.S. hospital-reported price transparency data to characterize prices for the most commonly billed chemotherapy drug administration Common Procedural Terminology (CPT) codes— 96413 (initial IV chemotherapy infusion) and 96415 (additional hour of IV chemotherapy). We obtained standard charges and commercial prices negotiated with private payers from hospitals that directly administer chemotherapy. To assess variation in prices, we calculated the ratio of the 90th percentile price to the 10th percentile price among private payers in each hospital and among hospitals in each Hospital Referral Region (HRR). We performed multivariable linear regressions to assess hospital, regional, and market factors associated with higher prices. Results: A total of 1,458 hospitals reported at least one price for CPT code 96413 or 96415. Hospitals reported 1 chargemaster and a median of 18 (IQR: 8–35) commercial prices negotiated with different private payers. National median commercial prices for CPT codes 96413 and 96415 were $536.00 (IQR: $326.43-$784.63) and $175.06 (IQR: $98.28-$327.25), respectively. Within each hospital, the 90th percentile commercial price was 2.2 times higher, on average, than the 10th percentile price for CPT code 96413, and 2.8 times higher for 96415. Among different hospitals within each HRR, the median commercial price at the 90th percentile hospital was 1.5 times higher than at the 10th percentile for CPT code 96413, and 2.3 times higher for 96415. On multivariable analysis, higher prices for CPT code 96413 were observed at for-profit hospitals ($215.12 higher than government not-for-profit hospitals, 95% CI: $55.22-$429.61). Higher prices for CPT code 96415 were observed at hospitals with higher predicted practice costs ($35.79 for every 1% increase in the geographical practice cost index, 95% CI: $16.69-$54.87), and a lower disproportionate share percentage ($0.96 for every 1% decrease in DSH patient percentage, 95% CI: $0.08-$19.41). Conclusions: Commercial prices for commonly billed IV chemotherapy infusions demonstrate significant variability. Prices for identical infusions vary by a factor of 2 depending on which hospital or private payer a patient selects. While prices for CPT code 96415 are largely explained by the relative cost of care, prices for the more expensive 96413 appear to be driven by the profit-status of the hospital. Further study is required to characterize the implications of such high levels of price variability on access to care and overall healthcare costs.
Telemedicine adoption and utilization among financially distressed patients with cancer during the COVID-19 pandemic: Insights from a longitudinal nationwide survey.
Authors: Hassan Abbas , Chu Carrie K. , Liu Jun , Angove Rebekah , Rocque Gabrielle Betty , Gallagher Kathleen D. , Momoh Adeyiza O. , Caston Nicole E. , Williams Courtney , Wheeler Stephanie B. , Butler Charles E. , Offodile Anaeze Chidiebele
Published: June 2022

1596

Background: Telemedicine use during the COVID-19 pandemic among financially distressed patients with cancer, with respect to the determinants of adoption and patterns of utilization, has yet to be delineated. We sought to systematically characterize telemedicine utilization in financially distressed patients with cancer during the COVID-19 pandemic. Methods: We conducted an analysis of survey data assessing the use of telemedicine in patients with cancer during the COVID-19 pandemic collected by Patient Advocate Foundation (PAF) from May 2020 to December 2020. Primary study outcome was telemedicine utilization rate. Secondary outcomes were independent predictors of telemedicine utilization patterns, volume, and utilization preferences. Multivariate and poisson regression analyses were used to identify predictive factors. Results: Of the 1,390 respondents, 627 completed two survey waves and were included in this study. Telemedicine adoption during the pandemic was reported by 67% of patients, with most (63%) preferring video visits. Younger age (odds ratio, 6.07; 95% CI, 1.47-25.1), and higher comorbidities (odds ratio, 1.79; 95% CI, 1.13-2.65) were independent predictors associated with telemedicine adoption. Younger age (19-35 yrs.) (incidence rate ratios [IRR], 1.78; 95%CI, 24-115%) and higher comorbidities (≥3) (IRR; 1.36; 95%CI, 20-55%) were independent predictors associated with higher utilization volume. As area deprivation index increased by 10 units, the number of visits decreased by 3% (IRR 1.03, 95%CI, 1.03-1.05). Conclusions: The rapid adoption of telemedicine may exacerbate existing inequities, particularly among vulnerable financially under-resourced patients with cancer. Policy-level interventions are needed for the equitable and efficient provision of this service.
Evaluation of tumor responses and overall survival in patients with recurrent glioblastoma (GBM) from a phase IIa trial of a CMV vaccine immunotherapeutic candidate (VBI-1901).
Authors: Wen Patrick Y. , Reardon David A. , Forst Deborah Anne , Lee Eudocia Quant , Haas Brittany , Daoud Teresa , Berthoud Tamara , Diaz-Mitoma Francisco , Anderson David E , Lassman Andrew B. , Iwamoto Fabio Massaiti
Published: June 2022

2014

Background: Cytomegalovirus (CMV) antigens have been reported in over 90% of GBMs. CD4+ and CD8+ T cells are most frequently directed against the gB and pp65 antigens, respectively, which are immunogenic targets in a CMV-based GBM immunotherapeutic. Methods: A total of 20 first-recurrent GBM patients were enrolled, with Karnofsky Performance Status of at least 70, across 2 arms of the Phase IIa extension phase to receive VBI-1901 (a gB/pp65 enveloped virus-like particle [eVLP]) adjuvanted with either GM-CSF (given intradermally) or AS01B (given intramuscularly) (NCT03382977). Patients were vaccinated with VBI-1901 every 4 weeks, with serologic immune-monitoring 2 weeks after each vaccination and surveillance brain MRI scans every 6 weeks. Results: 10 patients (6 women, 4 men) with a median age of 58 (33-67 yrs) were enrolled into the GM-CSF arm and 10 patients (3 women, 7 men) with a median age of 65 (40-67) enrolled into the AS01B arm. The 12-month OS rates for the GM-CSF and AS01B arms were 60% and 70%, respectively; the 18-month OS rate for the GM-CSF arm was 30%, and for the AS01B arm is expected to be 30%-40% (data has not yet matured). Two durable partial responses (locally determined by RANO) have been observed in the GM-CSF arm, with one patient progression-free and on protocol after 2 years with a tumor size reduction of 93% relative to start of treatment. Immunological analyses demonstrate that prolonged, monthly dosing with VBI-1901 does not lead to immunological tolerance. Dynamic boosting and loss in the peripheral blood of CMV-specific CD4 Tem cells after treatment with VBI-1901 formulated with GM-CSF may correlate with tumor responses. Conclusions: The U.S. FDA granted Fast Track Designation to VBI-1901 adjuvanted with GM-CSF in first-recurrent GBM patients, and an expansion of the ongoing trial with this formulation in this patient population, with the addition of randomization with a contemporaneous control arm, is anticipated to begin in H1 2022. Acknowledgement: GlaxoSmithKline Biologicals SA provided the AS01B adjuvant used in this study. Clinical trial information: NCT03382977.
Risk of intracranial hemorrhage with direct oral anticoagulants versus low molecular weight heparin in glioblastoma: A retrospective cohort study.
Authors: Reed-Guy Lauren , Desai Arati Suvas , Phillips Richard Edmund , Croteau Desiree , O'Neill Meghan , Albright Karen , Brem Steven , O'Rourke Donald M. , Amankulor Nduka , Bagley Stephen Joseph
Published: June 2022

2015

Background: Glioblastoma (GBM) is associated with a high rate of venous thromboembolism (VTE), but there is little data to guide anticoagulation in GBM patients, in whom the risks of VTE must be balanced against the risk of intracranial hemorrhage (ICH). Methods: We performed a single-institution retrospective cohort study of patients with GBM diagnosed with VTE from 2014-2021 who were treated with low molecular weight heparin (LMWH) or a direct oral anticoagulant (DOAC). The cumulative incidence of ICH was compared between the LMWH and DOAC groups. The primary outcome was clinically relevant ICH within the first 30 days of anticoagulation, defined as any ICH that was fatal, symptomatic, required surgical intervention, and/or led to cessation of anticoagulation. Key secondary outcomes included clinically relevant ICH within 6 months, fatal ICH within 30 days and 6 months, any bleeding within 30 days and 6 months, and recurrent VTE within 6 months. Fisher’s exact test was used for comparison of primary and secondary endpoints between the two groups. Cumulative incidence curves were generated using the Kaplan-Meier method, and the cumulative incidence of clinically relevant ICH at both the 30-day timepoint and 6-month timepoint was compared between the DOAC and LMWH groups using the Gray test to account for death as a competing risk. Results: A total of 121 patients were identified in the primary cohort for 30-day outcome analyses (DOAC, n = 33; LMWH, n = 88). For 6-month outcome analyses, the cohort included only patients who were maintained on their initial anticoagulant (DOAC or LMWH) and did not switch anticoagulants during the 6 months following diagnosis of VTE (DOAC, n = 32; LMWH, n = 75). The cumulative incidence of clinically relevant ICH at 30 days was 0% (0/33) in the DOAC group and 9% (8/88) in the LMWH group (p = 0.11). The cumulative incidence of clinically relevant ICH at 6 months was 0% (0/32) in the DOAC group and 24% (18/75) in the LMWH group (p = 0.001), with 4 fatal ICHs in the LMWH group. Other outcomes are displayed in the Table. Conclusions: Our study suggests that DOACs are associated with a lower incidence of clinically relevant ICH in patients with GBM-associated VTE compared to LMWH. These data support the use of DOACs as a safe alternative to LMWH in patients with GBM.[Table: see text]
Mebendazole in recurrent glioblastoma: Results of a phase 2 randomized study.
Authors: Menon Nandini Sharrel , Chatterjee Abhishek , Tonse Raees , Choudhary Amit , Mahajan Abhishek , Puranik Ameya , Sridhar Epari , Pathak Shruti , Jadhav Monica , Peelay Zoya , Walavalkar Rutuja , Kumar Hemanth , Krishna Madala Ravi , Chandrasekharan Arun , Pande Nikhil , Gupta Tejpal , Banavali Shripad Dinanath , Jalali Rakesh , Patil Vijay Maruti
Published: June 2022

2029

Background: Recurrent glioblastoma (GBM) has dismal outcomes and limited treatment options. Mebendazole (MBZ) is an anti-helminthic drug with in-vivo and in-vitro activity against glioma cell lines and has been demonstrated to be well tolerated in combination with lomustine (CCNU) and temozolomide (TMZ). In this phase 2 study, we sought to determine whether the addition of MBZ to CCNU or TMZ would improve overall survival (OS) in recurrent GBM. Methods: Adult patients with ECOG PS 0-3, with recurrent glioblastoma who were not eligible for re-radiation, were randomized 1:1 between CCNU-MBZ (n = 44) and TMZ-MBZ (n = 44). The primary endpoint was OS at 9 months, selected to reflect the BELOB trial. A 9-month OS of 55% or more in any arm was hypothesized to warrant further evaluation and a value below 35% was too low to warrant further investigation. Results: At 17.4 months, 68 events for OS analysis had occurred. The 9-month overall survival was 36.6% (95%CI 22.3-51) and 45% (95%CI 29.6-59.2) in the TMZ-MBZ and CCNU-MBZ arms respectively. ECOG PS was the only independent prognostic factor impacting OS (HR-0.478 95%CI 0.268-0.851; P = 0.012). Twenty-three patients (28.6%) enrolled had an ECOG PS 2-3 with inferior outcomes (median OS-5.67, HR-2.092 95%CI 1.175-3.731). Analysis restricted to ECOG PS 0-1 (n = 65) patients revealed a 9-month OS of 39.6% (95% CI 22.4-56.3) and 57.9% (95% CI 38.7-73) in TMZ-MBZ and CCNU-MBZ arms respectively. Grade 3-5 adverse events were seen in 8 (18.6%; n = 43) and 4 (9.5%; n = 42) patients in the TMZ-MBZ and CCNU-MBZ arms respectively. Conclusions: The addition of MBZ to TMZ or CCNU failed to achieve the pre-set benchmark of 55% 9-month OS. This was probably due to 28.6% of patients with poor PS of 2-3. In patients with ECOG PS 0-1, CCNU-MBZ had a 9 month OS of 57.9% and needs to be evaluated further. Clinical trial information: CTRI/2018/01/011542.
Population-based retrospective analysis of response assessment criteria in patients with glioblastoma.
Authors: Abbasian Parandoush , Ryner Lawrence , Lambert Pascal , Mann Anmol , Shankar Jai , Essig Marco , Pitz Marshall W.
Published: June 2022

2041

Background: Patients with glioblastoma are often treated with radiation and chemotherapy following surgery. Disease recurrence often occurs early in the disease course and during initial therapy, yet assessment of treatment response with MRI is highly variable in some situations. We sought to describe the clinical and imaging assessment and outcomes of an unselected cohort of patients with glioblastoma following the publication of the Response Assessment in Neuro-Oncology criteria. Methods: Patients diagnosed with glioblastoma in Manitoba, Canada, from 2012-2018 were identified from the Manitoba Cancer Registry. Chart review was performed to identify treatments given and decisions made by the treating team, and imaging analysis was performed to assess based on RANO and mRANO criteria. Determination of progression versus pseudoprogression according to these criteria was performed using clinical decision-making and review of follow-up imaging for confirmation. At time of the response assessment visit, patients were assessed by a primary oncologist (Radiation or Medical) and were also discussed at multidisciplinary Case Conference (comprised of Medical and Radiation Oncology, Neurosurgery, Neuropathology, and Neuroradiology). Treatment decisions were made with patient and primary oncologist, guided by input from the Case Conference. Tumour measurements were performed both in 2D using Product of Perpendicular Diameter analysis (PPD) and 3D volumetric measurements with/without necrotic region. Overall Survival (OS) and Progression Free Survival (PFS) were estimated to evaluate the effectiveness of response assessments and Kaplan-Meier method was used to compare the time to progression resulted from RANO, mRANO, and clinical impression. Results: A total of 285 patients were identified with a pathological diagnosis of glioblastoma. Of those, 199 (35% male, 65% female) were treated with concurrent temozolomide and radiation (75% 60Gy and 25% < 60Gy), and more than 90% went on to receive adjuvant temozolomide. Median Overall Survival of the 199 was 13.2 months. Of those treated with concurrent therapy, 122 (61%) had MRI studies with equivocal results within the first 6 months, with confirmatory MRI showing true progression in 73 (59.8%), pseudoprogression in 45 (36.9%), and 4 patients with undetermined outcome. Formal RANO and mRANO comparison is ongoing. Conclusions: Response assessment for patients with glioblastoma remains a frequent challenge despite the use of MRI and established response criteria, with more than half of patients having equivocal imaging changes and a high frequency of pseudoprogression.
A single-institution, retrospective examination of new contrast enhancement, progression, and pseudoprogression in IDH mutant glioma.
Authors: Wetzel Ethan , Eldred Blaine S.C. , Liu Vicki , Zapanta Rinonos Serendipity , Khanlou Negar , Liau Linda M. , Nghiemphu Phioanh Leia , Cloughesy Timothy Francis , Ellingson Benjamin M. , Lai Albert
Published: June 2022

2043

Background: IDH mutant glioma patients are followed by MRI, where new contrast enhancement (CEnew) is a hallmark of tumor progression. Interpretation of CEnew is confounded by pseudoprogression (PsP), the appearance of CEnew that spontaneously resolves on subsequent scans. PsP has been characterized in IDH wildtype patients, but is poorly understood in the IDH mutant category. This study represents an examination of the characteristics and impacts on patient survival of CEnew in IDH mutant gliomas. Methods: Of the 724 confirmed IDH mutant glioma patients treated at UCLA between 1998 and 2022, 587 were included (median follow-up = 5.23 years). Patients were excluded based on these criteria: <4 MRI scans, unknown IDH status, and unknown WHO 2016 diagnosis. CEnew was first identified by direct review of images and confirmed by the radiology report. Any new enhancement appearing on the first post surgical MRI was not considered CEnew. CEnew was interpreted as progression after surgical resection indicating tumor or the re-initiation of chemotherapy or radiation and was considered PsP after the resolution of enhancement without new treatment initiation. Some PsP patients could have received bevacizumab. Kaplan-Meier survival analyses were used to examine overall survival differences between groups. Results: 327 of 587 patients developed CEnew. The incidence of CEnew was higher in Grade 4 Astrocytoma (G4 Astro) versus all other pathologies and lowest in LO (p < 0.05). The Enhancement Free Survival (EFS) was shortest for G4 Astro patients (p =.002); LO patients had the longest median EFS of 2602 days (p = 0.002). The development of CEnew and presence of preoperative enhancement were both found to be negative survival prognosticators in all pathologies (p < 0.05). From our analysis, 92 patients developed PsP and 177 developed progression. The median duration of a PsP spot was 244 days. PsP spots appeared earlier than progression spots (median 538 vs 1113 days, p =.001). The incidence of PsP was highest in the G4 Astro group and lowest in LO patients. Survival analysis of patients with progression versus those with PsP and progression shows PsP is associated with longer OS in the entire cohort and the LO, AO, AA, and G4 Astro groups (p < 0.05). 100% of PsP patients received radiation therapy (RT). The median time from the end of RT to PsP was 209 days. Conclusions: While CEnew in IDH mutant gliomas is associated with reduced OS, poorer outcome is driven by progressors. PsP represents 28% of CEnew instances, typically occurs within 1 year of RT and have superior outcome to progressors and equivalent to of patients that do not display CEnew. [Table: see text]
Indirect assessment of tumor-infiltrating lymphocyte activity in serum for predicting outcome in patients with glioblastoma treated with immunotherapy in the recurrent setting.
Authors: Jensen Christina , Maarup Simone Bendix , Poulsen Hans Skovgaard , Hasselbalch Benedikte , Karsdal Morten A. , Svane Inge Marie , Lassen Ulrik Niels , Willumsen Nicholas
Published: June 2022

2059

Background: Glioblastoma (GBM) is an aggressive brain tumor and despite efforts in developing new effective therapies, patient survival remains low. There is increasing interest in using immune checkpoint inhibitors (ICIs) for GBM, however the immunosuppressive (cold tumor) characteristics of GBM limit the efficacy of ICIs. Consequently, there is a need to identify patients with active tumor-infiltrating lymphocytes (hot tumor). Several studies have shown that brain extracellular matrix such as type IV collagen has a dynamic composition with protease-induced alterations. In this study, we evaluated the clinical utility of a non-invasive biomarker of granzyme B degraded type IV collagen (C4G) reflecting tumor-infiltrating lymphocyte activity and of matrix metalloproteinase (MMP) degraded type IV collagen (C4M) in GBM patients treated with nivolumab (anti-PD-1) and bevacizumab (anti-VEGF) in the recurrent setting. Methods: C4G and C4M were measured in serum from 22 controls and 39 GBM patients previously treated with surgery, radiotherapy and chemotherapy in the primary setting. After GBM recurrence, 18 patients underwent salvage resection (arm A) however 21 patients had no possibility for resection (arm B). All patients were treated with nivolumab and bevacizumab (NCT03890952 phase II study). Baseline GBM samples were taken before the second-line treatment. The association between C4G levels and outcome was evaluated by Cox regression analysis for overall survival (OS) and odds ratio (OR) calculations for complete response (CR) rate after dichotomizing patients into low vs high levels of C4G (median cutpoint). Results: C4G (p = 0.004), but not C4M (p = 0.166), was significantly elevated in serum from GBM patients compared to controls. Moreover, patients with high C4G levels had a significantly increased likelihood of experiencing CR (OR=6.68, p<0.0001). Furthermore, patients with high C4G experienced improved OS compared to low C4G (HR=0.39), and this remained significant after adjusting for other significant risk factors (treatment arm and MGMT methylation) by multivariate analysis (HR=0.44) (table). Conclusions: A non-invasive biomarker reflecting tumor-infiltrating lymphocyte activity (C4G) has the potential to identify GBM patients responding to nivolumab and bevacizumab in the recurrent setting. In the future, this may provide a non-invasive biomarker tool for stratifying patients with GBM for ICI trials. Clinical trial information: NCT03890952. [Table: see text]
Treatment patterns of patients with glioblastoma multiforme in the real-world setting in a developing country.
Authors: Sánchez Hernández Juan José , Zarroca Palacio Santiago , Trejo Rosales Raul Rogelio , Remolina Bonilla Yuly Andrea , De Jesus Hernandez Dulce Angelica , Najar Miriam , Lizcano Aguilar Nestor Javier , Hernandez Castillo Marco Antonio , Cruz Andrea , Vélez Martínez Amairany Guadalupe , Sanchez Eduardo , Morales Hernández Karina , Irigoyen Álvarez Angel Gabriel Ignacio
Published: June 2022

2067

Background: Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor. Surgery followed of temozolomide administered concurrently with radiation therapy (RT) and followed by adjuvant temozolomide for six cycles significantly improved survival compared with radiation therapy alone in a randomized controlled trial published by Stupp and colleagues. Real world evidence in patients with GBM is scarce in Latin America. Methods: A retrospective study was conducted at the Hospital de Oncología, Centro Médico Nacional Siglo XXI, a referral center in Mexico City. We included histologically confirmed patients with GBM treated in a period from January 2015 to January 2019. Descriptive statistics and Kaplan-Meier method with log-rank were used for analysis. Cox regression was used for multivariate analysis. Results: A total of 184 patients were included, 96 were men (52,2%) and 88 were women (47.8%); median age was 56 years (range 18 - 87). ECOG performance status scale 0-1, and ≥ 2 represented 34.2% and 65.8% of the cohort, respectively. Maximal surgical resection was performed in 172 patients (93%). After surgery or biopsy, 12 patients (6.5%) did not receive any subsequent oncology treatment. Treatment with concomitant RT with TMZ was offered to 156 patients (84.4%) and RT alone to 16 patients (8.7%). The most common RT modality was conventional fractionation (60 Gy in 30 fractions) in 75% of cases. After concurrent therapy, 135 (86.5%) received adjuvant TMZ, of which 53.4% received ≤ 5 cycles and 46.6% received ≥ 6 cycles. The median overall survival of the entire cohort was 20.1 months (95% CI 13.3 - 26.9 months). Survival in patients with adjuvant TMZ was superior versus patients who did not receive complete multimodal treatment (26.3 months vs 10.5 months, p < 0.001). In the multivariate analysis, adjuvant chemotherapy was the only independent factor with statistical significance HR 0.18 (95% CI, 0.08 to 0.41 [p < 0.001]). Conclusions: In this retrospective study our data confirm that receiving adjuvant TMZ treatment is beneficial in prolonging overall survival compared to those who do not receive adjuvant therapy in patients with GBM.
The interim result of a phase I/II study of nivolumab with or without ipilimumab in combination with multi-fraction stereotactic radiosurgery for recurrent, high-grade, radiation-relapsed meningioma.
Authors: Huang Jiayi , Gao Feng , Shimony Joshua , Johanns Tanner Michael , Mantica Megan , Gershon Timothy Robin , Ney Douglas Edward , Tuncer Tolga , Mendez Joe Sammy , Streicher Howard , Campian Jian Li
Published: June 2022

2068

Background: There is a lack of effective therapy for recurrent high-grade meningiomas who relapsed after prior radiation therapy (RT). ETCTN 10186 is a phase I/II study to evaluate the feasibility and preliminary clinical efficacy of combining reirradiation using fractionated radiosurgery with nivolumab plus or minus ipilimumab for recurrent high-grade meningiomas. The preliminary results from the phase I portion are reported here. Methods: Recurrent grade II-III meningioma patients were treated with radiosurgery plus nivolumab with or without ipilimumab. Key eligibility criteria include age ≥ 18 years; ECOG score ≤ 2; tumor diameter 1-5 cm; prior radiation dose ≤ 70 Gy; normal organ function; no active autoimmunity. During the phase I portion, eligible patients were treated according to treatment-escalation schema following the modified 3+3 design (Table 1). The maximum tolerated combination (MTC) will be the regimen at which ≤ 1/6 patients experience dose-limiting toxicity (DLT) within 8 weeks of the start of study therapy. During the phase II portion, a total of 24 evaluable patients will be enrolled at the MTC using Simon’s MiniMax two-stage design. The primary endpoint of the phase I portion is to determine the MTC. Objective radiological responses (ORRs) are defined as per the Macdonald criteria. One cycle of immunotherapy is defined as 4 weeks of nivolumab with or without concurrent ipilimumab. Results: From 7/2019 to 3/2021, 13 patients were enrolled in the phase I, including 6 with regimen A and 7 with regimen B (Table). The median prior RT dose was 56 Gy (18-70) at a median interval of 2.8 years (1.3-13.3). There was no DLT in either cohort, so regimen B was deemed the MTC. The median cycles of immunotherapy completed were not significantly different between cohort A and B (11 vs. 6, p = 0.41, respectively). Three cohort A patients and 2 cohort B patients completed all planned doses of immunotherapy. Most patients stopped due to progression, and only one cohort B patient stopped due to treatment-related toxicity (grade 3 hypophysitis and encephalitis after 6 cycles of immunotherapy). After a median follow-up of 11.1 months, there have been 5 progressions and 4 deaths. The 6 month-PFS and 12 month-PFS rates are 62% and 54%, respectively. Two ORRs have been reported by institutional assessment, and central radiology review is ongoing and will be reported. Conclusions: Reirradiation using fractionated radiosurgery with nivolumab plus or minus ipilimumab are well tolerated for radiation-relapsed high-grade meningiomas. Phase II study of regimen B is currently enrolling. Clinical trial information: NCT03604978. [Table: see text]