bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved sensitivity in identification of first recurrences of metastatic breast cancer with a combination of cell and cell-free liquid biopsy analysis.
Authors: Di Caro Giuseppe , Bourdon David , Byun Jiyun , Singer Tatjana , Anderson Amanda , Blankfard Martin , Tubbs Alisa , Wenstrup Rick
Published: June 2022

e13003

Background: Liquid biopsy analysis detecting circulating tumor cells (CTC) or circulating tumor DNA (ctDNA) is a non-invasive approach that may provide clinically actionable information for patients’ (pts) treatment decisions when conventional biopsy is otherwise inaccessible or infeasible. Here we report a liquid biopsy method including CTC characterization & ctDNA alterations in pts symptomatic of first metastatic recurrence with a history of primary breast cancer (BC). Methods: Blood samples from 34 symptomatic BC pts were collected for cell & cell-free DNA analysis before undergoing contemporaneous tissue biopsy & initiating treatment for metastatic BC (MBC). Blood was also collected from 25 blood donors (HD) with no known cancer history. After plasma isolation, nucleated cells were plated, & slides were bio-banked. Immunofluorescent staining & subsequent imaging were performed on replicate slides. CTCs were identified using Epic Sciences digital imaging & machine learning algorithms trained to identify breast cancer cells. Single-cell (sc) isolation for genomic quantification of large-scale transitions (scLST) was used to further characterize individual CTCs. cfDNA from bio-banked plasma was analyzed to detect Class IA alterations in ctDNA. Results: Within this cohort of 34 patients, CTCs & ctDNA alterations were detected in 80% & 58%, respectively while no CTCs & ctDNA were detected in the HD cohort suggesting high specificity (100% & 100%). In this study, 26 pts were confirmed MBC (M1-BC) by tissue biopsy, 3 pts were non-MBC by tissue biopsy but still diagnosed as metastatic (Mx-BC), & 5 pts were confirmed non-MBC (M0-BC). To benchmark the cellular (CTCs & scLST+CTCs) & genomic (ctDNA) individual platforms, we designed thresholds of CTCs > 4, scLST+CTC+, & ctDNA+ that optimally identified M1-BC pts with high specificity (100%, 100%, & 100%) but low sensitivity (46%, 46%, & 50%). CTCs > 4 & scLST+CTC+ cutoffs had low concordance with the presence of ctDNA alterations, suggesting these platforms provide independent & complementary value when identifying MBC. To test this hypothesis, we designed combination models [CTC > 4][ctDNA+] & [scLST+CTC+][ctDNA+] that significantly improved sensitivity (75% & 67%) over individual platforms while maintaining high specificity (100% & 100%) when identifying the first recurrence of metastasis in BC pts. Conclusions: To our knowledge, this is the first report showing the additive & complementary value of models combining cellular & genomic liquid biopsy platforms for the detection of the first MBC recurrence. Our data suggest the clinical utility of combined CTC & ctDNA platforms for the identification of MBC when tissue biopsy is inaccessible or infeasible.
Safety, efficacy and survival outcome of Ado-trastuzumab emtansine (T-DM1) in patients with metastatic HER2-positive breast cancer: An Indian experience.
Authors: Gogia Ajay , Gupta Anshul , Deo S.V.S. , Sharma Dayanand , Mathur Sandeep
Published: June 2022

e13008

Background: Ado-trastuzumab emtansine (T-DM1) is the standard of care for patients with advanced HER2 positive breast cancer (BC) patients who progress on the first line anti-HER2 therapy or relapse within 6 months of adjuvant trastuzumab. There is a lack of data regarding the safety and efficacy of T-DM1 in the Indian population. Methods: This retrospective study aims to evaluate the efficacy and toxicity of T-DM1 in advanced HER2 positive female BC patients, registered at All India Institute of Medical Sciences, (AIIMS) New Delhi, India, between the years 2015-2021. The response was evaluated by Response evaluated Criteria in Solid Tumors(RECIST 1.1)guidelines. Progression-free survival (PFS) was calculated from the beginning of treatment with T-DM1 until disease progression or death from any cause. Overall survival (OS) was calculated from the beginning of treatment with T-DM1 until death from any cause. Results: This study included eighty patients with a median age of 49 years (27-73). Forty-four (55%) were premenopausal and hormone receptor positivity (either ER or PR) was found in 36 (45%) cases. The ECOG performance status was 0-1in 80% of patients. De- novo metastatic disease was found in 38(47.5%) cases whereas the remaining 42 (52.5%) patients were diagnosed with early or locally advanced disease and later become metastatic. The sites of metastasis were lungs in 26 (32.5%), brain in 23 (28.7%) liver in 23 (28.7%), bones in 18 patients (22.5%), lymph nodes in 15(18.7%), cutaneous and other rare sites in 8(10%) cases. All patients had received trastuzumab in the prior line of treatment and 18 (22.5%) patients had also received pertuzumab along with trastuzumab. The median number of T-DM1 cycles given was 9 (range 3-35). The overall response rate was 80%, 8(10%) achieved a complete response, 36 (45%) had a partial response, and 12 (15%) patients had stable disease. The Grade 3/4 toxicities were observed in 20(25%) cases and these were: thrombocytopenia 16 (20%), fatigue 10 (12.5%), transaminitis 10(12.5%), anemia 2 (2.5%), and peripheral neuropathy in 2 (2.5%) cases. Dose delay, interruption, and modification were observed in 25 (31.2%) cases. Within the median follow-up period of 18 months, the median PFS was 10 months and OS was 27 months. Hormone status (ER/PR) and prior pertuzumab therapy did not influence the outcome. Conclusions: This is the first study from the Indian subcontinent on T-DM1. It is safe and effective in our population and has shown comparable outcomes with the available literature however, higher rates of thrombocytopenia were observed.
Liquidscan mediated HER2 amplification detection in patient samples study.
Authors: Muller Rolf , Yeung Kay , Jones Stephenie , Brandt Christopher , Funari Vincent Anthony , Agersborg Sally , Muller-Cohn Judy , Dickerson Janet
Published: June 2022

e13016

Background: Overexpression of HER2 serves as an oncogenic driver in breast cancer which can result in tumor progression and distant metastases. Amplification or overexpression of HER2 occurs in approximately 15–30% of breast cancers and serves as a therapeutic, prognostic and predictive biomarker. There have been tremendous advances in HER2+ breast cancer management and there is an need to identify patients with HER2+ early breast cancer who may benefit from de-escalation or escalation of treatment. In addition, selection of HER2 therapies beyond the 2nd line setting for HER2+ metastatic breast cancer is currently unclear. Therefore, rapid monitoring tests for treatment response are needed. Liquid biopsy may provide a cost effective, sensitive, and non-invasive approach to monitor response. Methods: Whole blood (8ml) from 20 consenting patients with confirmed stage 3 or 4 metastatic breast cancer with clinical Her2 status identified by solid tissue biopsy (10 HER2+ and 10 HER2-) were collected. Circulating tumor cells were isolated on the LiquidScan system, were probed by HER2 FISH, analyzed using automated and visual microscopy. Results: Protocols were optimized to obtain morphology and cellularity of the tumor cells allowing conclusive HER2 identification for all samples. All samples from patients identified as Her2+ by standard invasive solid tumor biopsies could be identified (100% concordance), whereas for one sample that was reported as HER2-, cells were identified with the liquid biopsy having HER2+ FISH morphology. Further molecular analysis on this patient is under way. Conclusions: We were able to demonstrate that non-invasive liquid biopsy with the LiquidScan identifies HER2 status. The method has high concordance with conventional solid biopsy approach and may be a promising for patient monitoring. We will expand to larger sample sets to explore the full capacity of liquid biopsy to monitor and diagnose HER2 related diseases.
Platelet-to-Lymphocyte ratio (PLR) as a predictive marker in HER2 positive metastatic breast cancer patients treated with first-line trastuzumab therapy.
Authors: Fang Zi-Ru , Shen Xia-Bo , Wu Jia-Yi , Chen Ke-Yu , Shao Xi-Ying , Wang Xiaojia
Published: June 2022

e13024

Background: The immune system reveals to play a pivotal role in HER2 positive breast cancer responsiveness to trastuzumab therapy. The platelet-lymphocyte ratio (PLR) is representative blood markers of systemic inflammatory responses. It is suggested as an immunity biomarker in gastric, lung cancer and other cancers, but is less well known in breast cancer. The aim of this study is to investigate the predictive role of PLR in HER2 positive metastatic breast cancer patients treated with first-line trastuzumab therapy. Methods: This study retrospectively includes 287 HER2 positive metastatic breast cancer patients with first-line trastuzumab therapy in Cancer Hospital of the University of Chinese Academy of Science from January 2010 to November 2021. The Peripheral blood cell count of these patients before trastuzumab treatment is evaluated to calculate PLR. All patients are separated into PLRhigh or PLRlow cohort according to cut-off value defined as median value. Median value of PLR is 154.5, more than 154.5 is defined by PLRhigh, otherwise defined as PLRlow. Kaplan–Meier curves is performed to assess progression-free survival (PFS). Univariate and multivariate analyses were performed using a logistic regression model. Results: Of 287 patients, 228 patients’ peripheral blood cell count were available. 114 patients are PLRhigh and 114 patients are PLRlow. Patients with PLRhigh achieved a significantly worse PFS compared to those with PLRlow (median PFS: 8.47 months vs.9.92 months, HR:1.475, 95% CI:1.068-2.038, P = 0.014). Besides, mean corpuscular volume (< 89.2fL), lymphocyte (< 1.3), mean hemoglobin (< 30PG) are also related to worse PFS ( P= 0.003,0.033,0.055,respectively). Importantly, PLRhigh, mean corpuscular volume, remain independent predictors in the multivariate COX analysis (HR 0.689,95%CI 0.493-0.962, P = 0.028;HR1.646,95%CI 1.177-2.302, P = 0.004). Conclusions: Patients with pre-treatment PLRhigh showed less sensitivity to trastuzumab therapy for metastatic breast cancer patients independent of other molecular characteristics. The pre-treatment PLR levels might serve as a predictive biomarker for HER2 positive breast cancer with trastuzumab therapy.
Treatment sequence for hormone receptor-positive HER2-negative advanced breast cancer: Results of a retrospective analysis of Russian patients diagnosed with aBC in 2014-2021.
Authors: Stenina Marina , Zhukova Lyudmila , Stroyakovskiy Daniil , Karaseva Vera V. , Tjulandin Sergei
Published: June 2022

e13032

Background: CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have dramatically changed therapeutic landscape of hormone receptor-positive HER2-negative advanced breast cancer (HR+ HER2- aBC). There are three iCDK4/6 in Russia, which are available and included into the clinical guidelines as a preferred first line treatment option beginning since 2018. The aim of this study was to assess evolution of treatment approaches to HR+ HER2- aBC and identify demographic and disease characteristics in correlation with available groups of therapy (chemotherapy, endocrine therapy ±mTOR inhibitors/ CDK4/6i). Methods: Аdult patients diagnosed with de novo or recurrent HR+ HER2- aBC in 2014-2021 identified in outpatient departments of Moscow state oncology hospitals were included into our non-interventional, descriptive, retrospective cohort study. Primary objective of this real-world study was to describe the rate of CDK4/6i usage in the first line setting. As a secondary objective, we describe patient and disease characteristics in iCDK4/6 group, as well as in the endocrine monotherapy and chemotherapy groups. Results: From the cohort of 1000 patients (full-set analysis population) 874 cases were selected, who received treatment since 2018. 45.9% (95% CI 42.6, 49.2) patients were treated with CDK4/6i in combination with endocrine therapy in the first-line setting. From them in the subgroups of patients with or without visceral metastases 50.5% (95% CI 45.5, 55.5) and 42.1% (95% CI 37.7, 46.5) were treated with CDK4/6i in the first line setting, respectively. Among 874 cases 78.0% (95% CI 75.3, 80.7) patients received endocrine therapy ± targeted therapy; in the subgroups of patients with or without visceral metastases 69.5% (95% CI 64.9, 74.1) and 84.9% (95% CI 81.7, 88.1) were treated with endocrine therapy ± targeted therapy in the first line setting, respectively. Conclusions: Endocrine therapy is a predominant therapeutic option in the first line setting for HR+ HER2- aBC. Clinical trial information: NCT04852081. [Table: see text]
Factors associated with CDK 4/6 inhibitor use for patients with advanced, hormone positive, HER-2-negative breast cancer.
Authors: Weldon Christine B. , Trosman Julia R. , Li Xi , Gradishar William John
Published: June 2022

e13038

Background: “CDK4/6 inhibitors have emerged as a standard of care for patients with HR-positive, HER2-negative advanced breast cancer.” Wayne Kuznar ASCO Reading Room 10.29.2019. Within an academic institution there were concerns that CDK 4/6 inhibitors were not utilized as indicated. We conducted an analysis of CDK 4/6 inhibitor use for patients with advanced, hormone positive, HER2 negative breast cancer to assess factors associated with CDK 4/6 inhibitor use. Methods: We conducted a retrospective medical records review of patients treated at an academic medical center from 01/1/2015 to 9/30/2020 with stage IV, hormone positive and HER2 negative breast cancer. We compared characteristics for patients that received one or more CDK 4/6 inhibitors to those who did not receive any CDK 4/6 inhibitors. Statistical analysis used Fishers exact 2-sided test via GraphPad QuickCalcs website. Results: 162 patient records met inclusion criteria, 73% (119/162) received one or more CDK 4/6 inhibitors as part of their care. The average age of patients who received CDK 4/6 inhibitors was 59.9, as compared to 66.9 average age in patients who did not receive CDK 4/6 inhibitors. Patients who received CDK 4/6 inhibitors were more likely to have received chemotherapy (Table, p < 0.0001), have a family history of cancer (p < 0.0001) and have a Charlson comorbidity index of 5 or more (p = 0.0005). Patients receiving CDK 4/6 inhibitors trended more likely to have used tobacco at some point (p = 0.09). Patients who did not receive CDK 4/6 were more likely to have refused, moved or be in hospice (p = 0.003). There were no statistically significant differences based on patient status, timing of diagnosis or timing of first hormone receptor positive dose. Further analysis of the 27% (43/162) of patients not receiving CDK 4/6 inhibitors identified that 40% (17/43) died, 28% (12/43) had Charlson comorbidity score of 7 or more, 19% (8/43) refused treatment. The remaining 14% (6/43), 4% (6/162) of entire population, did not have a clear reason for not getting CDK 4/6 inhibitors, of those 4 received hormone therapy, 1 received chemotherapy and 1 received both. Conclusions: In a retrospective analysis of patient records, we found consistent use of CDK 4/6 inhibitors for indicated patients. Patients who did not receive CDK 4/6 inhibitors died, had a high co-morbidity index, or refused treatment. Only 4% of the population analyzed did not have a visible reason to not receive CDK 4/6 inhibitors.[Table: see text]
Comparison of DNA sequencing, immunohistochemistry, and in-situ hybridization techniques to determine HER2 status in metastatic breast cancer patients.
Authors: Lal Lincy S. , Milne Dana , Walker Mark S. , Kovach Marina
Published: June 2022

e13045

Background: Limited studies exist comparing methods for HER2 status determination using real-world data (RWD). Results of metastatic breast cancer (MBC) patients with Next Generation Sequencing (NGS) within the ConcertAI Genome360 dataset with DNA sequencing were compared to the standard immunohistochemistry (IHC) or in-situ hybridization (ISH) or both IHC and ISH for HER2 status. Methods: Patients diagnosed with MBC, with HER2 status determined with NGS DNA sequencing, IHC, or any of the ISH tests, by various laboratories within 2 months of each other, from August 19, 2011 to March 9, 2021, were analyzed. Patients were classified as positive, negative, or equivocal based on each of the testing methods. Comparisons were made between DNA sequencing and IHC results, DNA and ISH results, and DNA and IHC and subsequent ISH results. Results: The study sample included 252 patients (99% female, mean age [SD] of 62 [11.93]) with 382 test combinations as follows: 220 (58%) with DNA sequencing and IHC results, 127 (33%) with DNA sequencing and ISH results, and 35 (9%) with DNA sequencing and IHC and ISH results. Of the 220 combinations with DNA sequencing and IHC results, 15 were uniformly considered HER2+, 160 HER2-, and 1 equivocal, while 44 differed in the results, resulting in 80% match rate. Of the 127 combinations with DNA sequencing and ISH results, 14 were HER2+ and 96 HER2-, while 17 differed, resulting in 87% match rate. Of the 35 combinations with DNA sequencing and IHC and ISH, 3 were HER2+ and 26 were HER2-, while 6 differed, resulting in 83% match rate. Match rate was significantly higher for patients with negative results, than positive results. Specimen type, site, and type of expression had no impact on match rates. Conclusions: RWD indicate relatively high level of match rate among DNA sequencing, IHC, and ISH results in MBC patients. However, 13-20% of the combinations did not match. For these patients, mechanisms to reach consensus need to be explored to determine optimal treatments.
Clinical outcome and characteristics of Turkish breast cancer patients during SARS-Cov-2 pandemic: Single center experience.
Authors: Isıklar Aysun , Soyder Aykut , Gumusay Ozge , Basaran Gul
Published: June 2022

e13049

Background: COVID-19 pandemic has placed an unprecedented burden on health care system. Patients with cancer are reported to have a higher risk of infection and a more complicated COVID-19 course. Breast cancer (BC) is the most common cancer in women in Turkey. We aimed to evaluate the clinical outcome of breast cancer patients who had a diagnosis of COVID-19. Methods: Medical records of breast cancer patients who had COVID-19 between July 2020-2021 at our center were retrospectively rewieved. We recorded pathological, clinical, treatment characteristics, and the clinical outcome of COVID-19 infection. Results: A total 82 breast cancer (BC) patients had COVID-19 between July 2020-2021. All patients were female, with a median age of 49 (43-64 years). Eighty-five % of all patients had early and 14.6% had advanced stage BC. COVID-19 had a mild clinical course in 73%, hospitalization was required in 27% of patients. Twenty-five patients who required hospitalization were discharged. Three (3,6%) patients who had heavily pretreated metastatic breast cancer, required ICU and died due to COVID-19. Metastatic disease (p 0.002) and chemotherapy within 7 days of COVID-19 diagnosis (p = 0.024) have been associated with increased mortality. Conclusions: In our breast cancer cohort, most patients had a mild COVID-19 course. Advanced disease and chemotherapy within 7 days of diagnosis were the two risk factors for increased mortality.
Risk of seizures in a population of women with BRCA-positive metastatic breast cancer in the United States.
Authors: Sebby Wendy , Kilpatrick Ryan , Mazumder Debasish , Ghosh Anirban , Papademetriou Eros , Potluri Ravi , Liede Alexander
Published: June 2022

e13056

Background: Real-world evidence on the risk of seizures in subgroups of women with advanced breast cancer (BC) across treatment-related or clinical subtypes is limited. A large electronic health record (EHR) dataset was used in this study to measure incidence and risk factors for seizures among women diagnosed with BRCA-associated metastatic BC (mBC). Methods: We used the Optum EHR database, which includes natural language processing (NLP) abstracted details from physicians’ notes, to identify a cohort of females with mBC (based on secondary malignancy ICD-9/-10 codes or NLP) diagnosed between 2008-2018 with 12 months of pre-index history, evidence of BRCA mutation positive (BRCA+) status, and no history of prior cancers. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR-, HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC). Incidence of seizures was measured using diagnosis codes and NLP, and incidence rates were calculated as the number of women with a seizure over the period from metastasis to first seizure or the end of follow up. Incidence rates were also measured across the following risk factors: PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsant use before BC diagnosis, while controlling for age at metastasis, number of prior lines, and metastasis location. Results: Of the 7,941 BRCA+ patients identified, 27.8% had ≥1 seizure during mean follow-up of 2.35 years, with an incidence rate of 11.83 (95% CI: 11.35-12.33) per 100 person-years. The HER2-/HR+ and TNBC subgroups had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). Kaplan-Meier analysis of time to seizure showed that HR- phenotype was associated with a longer time to first seizure. Patients with diagnosed brain metastases or a history of seizures had higher seizure incidence rates compared to patients without the respective risk factors (42.55 [95% CI: 28.59-63.30] vs 5.26 [4.20-6.59] and 34.76 [23.24-52.01] vs 6.35 [5.11-7.88]). Incidence trended higher with PARP inhibitor use, but patient numbers were low. Conclusions: Using both diagnosis codes and NLP, this study shows that seizures occur frequently in women with BRCA+ mBC, even those without diagnosed brain metastases. The seizure incidence rates by phenotype underscore their relevance when assessing seizure risk. These findings may have implications for clinical practice and for assessing benefit-risk ratios of novel agents.[Table: see text]
A preliminary review of adoption of new HCPCS codes for NGS in CMS claims.
Authors: Smart Dave , Moore Wendy , Fosvig Susanne Munksted , Bloom Kenneth Joel
Published: June 2022

e13522

Background: Adequate reimbursement is considered a prerequisite for adoption of new diagnostic technologies that facilitate patient access to better treatments. Detailed longitudinal investigation of the adoption of new HCPCS codes and the factors influencing it are scarce, although the availability of large-scale claims databases should facilitate such studies. We examined claims for three CPT codes used for next generation sequencing (NGS): 81445, 81450 and 81455 in a large database of claims data from CMS and attempted to correlate presumptive drivers of test adoption such as coverage decisions and payments with test volume. Methods: CMS claims data were accessed using CMS’ Virtual Research Data Center (VRDC) under data use agreement 50486. Any claim with a CPT code of 81445, 81450 or 81455 was extracted from the data and analysed using SAS Enterprise Guide with results summarised in Microsoft Excel. Data relating to national/local coverage determinations were located by internet searches. Results: Test volumes for all 3 codes showed significant variability, including a large decrease around Q1-2 of 2020, likely due to the COVID-19 pandemic. Utilization of the 3 CPT codes varied by patient diagnosis. Details of the top 5 diagnoses for each CPT are given in the Table. The top 30 diagnoses for each CPT code accounted for 80.33%-88.45% of patients. Conclusions: Utilisation of NGS testing from 2016-2021 was highly variable, confounding attempts to match potential drivers to changes in monthly test volumes. A relatively small number of conditions accounted for >80% test use. Increased use of 81445 and 81450 from 2019 onwards may be related to CMS LCD issued in March 2018, suggesting that it can take 8-9 months or more for a LCD to filter through to testing practice. Decreases in test volume around March 2020 coincide with decreased patient presentation and testing for cancer because of the COVID-19 pandemic indicating that factors beyond reimbursement can significantly affect test use. Changes in reimbursement or adoption of proprietary lab analysis (PLA) codes covering specific NGS tests may have caused the drop in test volumes in the latter half of 2021. This study demonstrates that determination of factors affecting adoption of a test technology can be problematic due to wide variation in claims over a relatively short space of time. However, determination of these factors is important as they ultimately affect patient access to testing and potentially to therapy. [Table: see text]
Preoperative anemia in gynecologic oncology surgery: Analysis of the National Surgical Quality Improvement Program Database.
Authors: Cain Abigail , Galvan-Turner Valerie Bianca
Published: June 2022

e13528

Background: Preoperative anemia has been identified as risk factor for adverse postoperative outcomes following hysterectomy for benign indications. However, studies have not yet been performed looking at the effect of preoperative anemia on women undergoing surgery for a gynecologic malignancy. Methods: We used the National Surgical Quality Improvement Program data from 2014 to 2019 to conduct a retrospective, population-based cohort study. Our exposure of interest was preoperative anemia, defined as a hemoglobin value <12 g/dL and stratified using the National Cancer Institute grading system. We preformed a logistic regression was used to calculate the adjusted odds ratio evaluate the effect of anemia on the outcomes. Results: Of the 54,569 women in the cohort, 13,232 (24.2%) had anemia. Conclusions: Preoperative anemia, at any grade, is associate with an increase in postoperative morbidity and that the effect is increased with worsening grade of anemia.[Table: see text]
Code status discussions in outpatient setting.
Authors: Prasad Sonika , Jain Nikita , Tahir Nayha
Published: June 2022

e13539

Background: In the face of the COVID 19 pandemic, goal-concordant care has been gaining further significance. Discussions about the care goals are best when they are exploratory, conversational, and longitudinal. Complex information processing is best done outside of a crisis. Ideally, these conversations should start with the primary care clinician who has a longitudinal clinical relationship with the patient. Methods: A quality initiative project was conducted at the Internal Medicine Residency Clinic located in Northwestern Medicine Woodstock Hospital. Review of order entry in electronic medical records and charts for code status was assessed for data gathering. Patients above the age of 65 years presenting for their annual physical visit were included in the study. Various interventions were done, including educating residents through didactic lectures, sending electronic reminders to the residents and formatting a template note including code status documentation. Pre and post-intervention data was gathered. Results: A total of 104 patients were in the pre-intervention group and 94 patients in the post-intervention group. Pre-intervention, code status was addressed in 33% of total patients interviewed during their annual physical visit. Post intervention, code status was addressed in 48% of the patients. Conclusions: This project was undertaken to increase awareness on a crucial aspect of the addressing code status in outpatient setting. Post intervention studies showed that addressing code status significantly increased. In order to fill the gap, we propose that addressing code status be a mandatory process or a reminder be generated in electronic health records.
Predicting immune checkpoint inhibitor-related hepatitis using electronic health records of patients.
Authors: Horváth Gergely , Kiss Zoltán , Csernai Eszter , Lippenszky Levente , Napan-Molina Pablo , LeNoue-Newton Michele , Mittendorf Kathleen , Smith David , Park Ben Ho , Wolber Jan , Osterman Travis John
Published: June 2022

e13564

Background: Immune checkpoint inhibitor (ICI) therapies have shown impressive results in treating oncology patients. However, some patients exhibit immune-related adverse events (irAE-s), one significant irAE is autoimmune hepatitis. Oncologists routinely screen for hepatic toxicity with a complete metabolic panel prior to each ICI administration. Predictive modeling of irAE-s based on patient factors has the potential to help guide treatment selection and monitoring protocols. We have developed a widely usable model based on patient history and routinely collected standard blood panels that can predict whether a patient will experience hepatitis with ICI administration. Methods: We defined irAE hepatitis as any single value of AST, ALT, or alkaline phosphatase three-times the upper limit of normal (ULN) as following ICI treatment. The goal was to determine whether the level of the biomarkers exceed this threshold within certain, pre-defined time-windows, as determined by medical experts. We used feature engineering to compress the time-series of lab panels into single meaningful statistical descriptors, such as mean or maximum of these vectors. The dataset was highly unbalanced with many more negative cases (out of the 3231 patients, depending on the window length used for feature generation, 100-400 positives were found), which warranted the application of synthetic resampling methods. Finally, we trained various ensemble models ( e.g., random forest, gradient boosting), on both the resampled and original dataset, to obtain the final, predictive model for the likelihood of irAE hepatitis. Models were tuned to favor high recall and lower precision (identification of patients for increased monitoring) or moderate recall and moderate precision (maximizing F1-score). Results: We explored several modelling methods, such as KNN, Logistic Regression, Random Forests (RF), Gradient Boosting (GB), and stacking. GB without resampling produced the best model with the moderate recall and precision. To achieve high recall with low precision, we needed to resample the dataset with random majority class under sampling and then use RF (see table below for exact results). Conclusions: In this study, we show contemporary machine learning methods can be used as a screening tool for patients at risk for irAE hepatitis. This method could be used to identify patients who would benefit from additional laboratory monitoring between ICI administrations or guide clinical decisions about therapy cessation in advance of toxicity. Additionally, these methods may be further developed and adapted to improve clinical trial exclusion criteria for patients most likely to develop irAE hepatitis.[Table: see text]
Prospective evaluation of an affordable and portable artificial intelligence-based modality for breast cancer screening in women across breast densities.
Authors: Bansal Richa , Aggarwal Bharat
Published: June 2022

e13585

Background: Mammography is known to be less effective in women with dense breast. Thermalytix is a radiation-free technique for breast screening which uses artificial intelligence over thermal images and has shown promising results in early clinical results. Methods: A prospective, cross-sectional study was conducted from December 2018 to January 2020 to compare the performance of Thermalytix with Mammography in women with dense and non-dense breast tissue. Women aged between 30 and 80 years who presented for a routine health check-up to the hospital and provided informed written consent for the study were included in the evaluation. All women took both Thermalytix and 2D-mammography tests. The output of the Thermalytix tool was blinded to the radiologist interpreting mammograms and the Thermalytix technician did not have access to any other imaging reports of the patient . For participants who were reported as positive on either or both of the tests, confirmatory diagnostic investigations were recommended; the outcome of which was used as the ground truth for comparison. Sensitivity and specificity of the two tests were calulated across age-groups, menopausal status, and breast densities.. Results: Among the 687 women invited for the study, 459 women fulfilled the inclusion criteria for the study analysis. Overall, 21 women were diagnosed with breast malignancies in the study. Thermalytix demonstrated an overall sensitivity of 95·24% (95% CI, 76·18-99·88) and a specificity of 88·58% (95% CI, 85·23-91·41). In 168 women (36·6%) who had ACR categories ‘c’ or ‘d’ dense breasts, Thermalytix showed a sensitivity of 100% (95% CI, 69·15-100) and specificity of 81·65% (95% CI, 74·72-87·35). Among these 168 women, 37 women had an incomplete assessment (BI-RADS 0) of their mammograms with a single reader (trained radiologist), while all 3 malignancies in these women were identified by Thermalytix tool. Conclusions: Thermalytix has the potential to be a radiation-free, privacy-conscious modality for breast cancer screening. Particularly in women with dense breast tissue, it can be a supplemental modality to mammography. As an automated, portable and affordable solution, Thermalytix test could be used alone for large-scale breast cancer screening programmes in resource-constrained settings. Clinical trial information: NCT04688086.
Combination dose finding trials for targeted/immuno oncology agents in early development: Lessons learned.
Authors: Zhou Li , Reddy Micaela , Mittapalli Rajendar K. , Yang Jing , Yin Donghua
Published: June 2022

e13595

Background: Combination therapy is commonly evaluated in clinical development of oncology investigational agent (IA). An IA may be combined with an approved agent (AA), or with another IA. The aim of this landscape analysis was to 1) summarize and evaluate the different dose finding study design options used in early clinical development for oncology targeted/immuno therapy combinations; 2) propose best-fit application scenarios for each trial designs. Methods: The data sources included 1) FDA approved oncology combination therapies from 2010 to 2021; 2) registered early-stage oncology combination trials in the US with protocol available at clinicaltrial.gov from 2015 to mid-2021; 3) Pfizer internal programs. This analysis focused on “IA + IA” and “IA + AA” combinations. We extracted data on modality type, target, starting dose rationale, trial design and approved dose (if applicable) of the combination. Starting dose considerations and pros/cons of different trial designs were assessed. Results: Both external and internal in scope trials were summarized, including 8 approved non-Pfizer oncology combinations, 32 clinicaltrial.gov registered external trials and 14 Pfizer internal programs. Most surveyed combination trials included an AA. Selection of starting doses and dose escalation design for the combination were the two critical factors influencing the efficiency of clinical development (time, cost and resources). Overlapping toxicities are key concerns resulting in more conservative combination starting doses. The combination dose finding was generally performed with one of the following designs: sequential design, parallel (staggered) design, healthy volunteer first-in-human single ascending dose before first-in-patient combination and monotherapy lead-in (intra-patient “crossover”). A comparison of the characteristics of these dose finding designs indicate that the choice of a particular design should consider factors including exposure-response relationships for efficacy and safety of both monotherapy and combination, the benefit/risk to trial participants, study population, etc. We proposed application scenarios for each trial designs by incorporating the above considerations and analyzing the collected trial examples in the database. The dose finding for combinations between two IAs should consider additional factors including the relative contributions of the two agents to efficacy and safety, the anticipated minimal dose/exposure level for efficacy, and potential pharmacokinetic/pharmacodynamic drug-drug interactions. Conclusions: Multiple design options for dose finding exist for oncology targeted/immuno therapy combinations involving IA. The choice of a suitable design should consider properties and available data of each agents involved, trial efficiency, as well as benefit/risk of trial participants and target indication.
A remote evaluation of NAVIFY guidelines using simulation-based research methods.
Authors: Halligan Jack , Prime Matthew Stewart , Fontana Gianluca , Guo Chaohui , Andoni Anna , Ghafur Saira
Published: June 2022

e13605

Background: This pilot study was designed to explore the use of remote simulation-based research methods to assess NAVIFY Guidelines, including data collection procedures. NAVIFY Guidelines is a software application that digitizes NCCN Guidelines and allows the user to navigate guidelines in a stepwise manner to support clinical decisions. The application has been designed to simplify access and improve adherence to guidelines in the management of oncology patients. Methods: A total of 10 board-certified oncologists were recruited to participate from large academic centers (5), community hospitals (3) and specialist oncology centers (2). Each oncologist reviewed clinical information for 10 synthetic breast cancer patient cases (i.e., 100 case reviews). The cases were developed by a medical oncologist, a surgical oncologist, a radiologist and a histopathologist. Participants were tasked to select the most appropriate clinical decision as per guidelines in two conditions: 1) using a PDF of the NCCN Guidelines (control), and 2) using NAVIFY Guidelines (experimental). Outcome measures were compared across conditions. Sessions were conducted via Google Meet, with participants using the share screen feature to allow the session to be recorded. The cognitive burden of each method was measured via a psychometric test conducted before and after each method (the Stroop Colour and Word Test). After each session, a post-simulation survey gathered feedback on 1) study methods, 2) use of synthetic patient cases, 3) workload effort required (via the NASA Task Load Index), and 4) usability of NAVIFY Guidelines (via the System Usability Scale). A short interview was conducted after each session to gather feedback on the benefits and challenges of using NAVIFY Guidelines and to discuss the participant’s experience of the simulation session. Results: All data collection procedures were successful including 1) assessment of time taken to reach a clinical decision, 2) psychometric testing, 3) survey data, and 4) user feedback. All participants felt the synthetic patient cases were either ‘very similar’ (7 of 10) or ‘somewhat similar’ (3 of 10) to cases seen in routine clinical practice, and the majority felt the task completed during the sessions was ‘very similar’ (3 of 10) or ‘somewhat similar’ (4 of 10). Conclusions: Remote evaluations can be conducted quickly helping to keep pace with product development cycles. The method is easily repeated therefore supporting evaluation of product development over time. In addition, managing simulations remotely enables the possibility of simultaneous evaluations across multiple geographies, and the use of synthetic patient data eliminates data protection concerns. This study suggests that simulation-based research can be used to assess digital health solutions remotely in a timely fashion.
Feasibility study of integrated ePROs in routine care during radiation therapy for head and neck cancer.
Authors: Katzel Jed Abraham , VanDenEeden Stephen K. , Liu Raymond , Leimpeter Amethyst D. , Briones Cecilia B. , Lewis Dionne L. , Lee-Enriquez Nancy M. , Yan Jennifer M. , Altschuler Andrea , Gillis Amy M. , Patel Deep , Patel Milan Dilip , Kaufman Marcy Ann , Shan Jun , Basch Ethan
Published: June 2022

e13612

Background: Use of electronic Patient Reported Outcomes (ePRO) tools in the routine care of cancer patients remains challenging despite data showing that they can improve resource utilization and patient outcomes. Patients with head and neck cancer during intensive therapy with radiation therapy (RT) may particularly benefit from interventions focused on early symptom management. Methods: 34 patients with head and neck cancer were enrolled in an implementation study and received ePROs integrated within the electronic medical record (EMR) weekly during radiation therapy (RT) within a large integrated health care delivery system. ePROs consisted of the FACT G7 and FACT-HN. After completion of each survey on the patient portal, a radiation oncology RN documented any abnormal findings and subsequent interventions using a standardized format within the EMR. If patients did not have access to the patient portal or had language barriers, they could complete ePROs with a translator by phone or video. Results: Between January and December of 2021, 34 patients with head and neck cancer receiving curative RT were enrolled. The median age 65 years (range 46-84). 74% of patients were male. 59% were white, 26% Asian/PI, 5% Black, and 5% Hispanic. The most common primary cancer sites were: oropharynx (32%), nasopharynx (24%), larynx (18%), oral cavity (9%). 65% of patients received concurrent chemotherapy with RT and 35% received RT alone. 97.4% of patients had access to the online portal. The total number of surveys completed was 194 with a median of 7 per patient (range 1-8). There was a total of 887 abnormal findings reported and 887 documented and corresponding interventions resulting in a 100% intervention rate. Over the course of RT the mean number of abnormal findings increased from 2.26 at baseline (n = 34) to 6.27 at week 7 (n = 24), P < 0.0001. Hospitalizations and Emergency Department (ED) visit data were collected during the study and up to 30 days from last day of RT. There was a total of 2 hospitalizations and 8 ED visits. Conclusions: ePROs integrated within the patient portal and EMR are feasible during RT for patients with head and neck cancer within a large integrated health care system. The use of ePROs integrated within the patient portal and EMR can lead to a high rate of intervention. The increasing number of abnormal findings on ePRO during intensive treatment for head and neck cancer is consistent with known patterns of toxicity and confirm the value of studying methods for improving quality of life in this patient population.[Table: see text]
Seroconversion following first and second dose of COVID-19 vaccination among cancer patients: A prospective longitudinal observational study from India on the effectiveness of COVID vaccines.
Authors: Kalpathi Krishnamani Iyer , Pappala Raj Kishore , Nawaz Ayesha , Krishnamani Mithra , Mathi Kavita
Published: June 2022

e13629

Background: Cancer patients are at high risk of infections and vaccination against SARS CoV-2 virus is essential to reduce the risk of COVID-19 and its complications. Different types of vaccines against SARS CoV-2 have been developed at record speed, followed by emerging efficacy studies of these vaccines. Our aim is to assess the efficacy of these vaccines in Indian cancer patients, along with factors such as intervals between doses impacting a robust immune response. Methods: A longitudinal observational study was done to evaluate the seroconversion post one and/or two doses of ChAdOx1 nCoV-19 (Covishield) and BBV152 (Covaxin) vaccine in adult cancer patients. Patients received 0.5 ml of vaccine 4 – 12 weeks apart based on existing Government regulations. A minimum gap of four weeks post vaccination for sample collection was followed. Samples were collected during patient follow up or treatment schedules. The control group comprised of healthy volunteers. Our primary endpoint was to assess seroconversion rates to SARS COV-2 spike protein after first and/or second dose. Our secondary endpoint was to explore the factors influencing seroconversion and to compare the two available vaccines in India, Covishield and Covaxin. Results: Between May 1, 2021 and January 16, 2022, antibody levels were measured in 219 patients after second dose and 56 patients after each dose. The mean age was 57.6+12.2 years (24-85 years) with 52% above 60 years age, and 68% being women. Most common cancer was breast (39.3%) followed by GIT (17.4%), while 44% had metastatic disease. Overall, 54.3% had not received any systemic therapy in the past 6 months, while 22.4% had received chemotherapy and 14.2% had received biologics. Three fourth of the patients had received Covishield and the rest Covaxin. Amongst the 56 patients who had antibody testing after both doses, seroconversion after first and second dose were 85.7% and 96.4% respectively. Higher seroconversion was seen in younger age group, treated with biologics without chemotherapy. In 219 patients, post second dose, seroconversion was marginally higher in women compared to men (96.6% vs 91.4%), on biologics (96.8%) when compared to patients taking chemotherapy (89.8 %), although not statistically significant. Overall patients on Covishield vaccine showed higher seroconversion, compared to Covaxin (P = 0.002) (OR- 5.9). Timing of antibody sample had no effect on seroconversion. Conclusions: Both Covishield and Covaxin are immunogenic in cancer patients. Seroconverison after first and second doses were 85.7% and 96.4%with higher rates amongst patients on biologics compared to chemotherapy. We are hoping to continue our study longitudinally to further explore factors impacting efficacy amongst these two vaccines.