bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-reported and clinical outcomes among patients with pancreatic cancer.
Authors: Pichardo Rayli , Jacob Brigid , Jamil Maria , Jamil Dawood , Raslan Shahm , Rose Courtney M. , Adjei Boakye Eric , Poisson Laila , Tam Samantha , Philip Philip A.
Published: June 2024

e23200

Background: Pancreatic cancer is associated with poor survival, high symptom burden, and psychological distress. Conventional assessments such as performance status (PS) have relied on provider-generated data to evaluate the selection of treatment and prognosis. Patient-reported outcome measures (PROMs) represent a patient-centric representation of the patient experience and are increasingly applied as tools to help improve outcomes and quality of life. However, little is known about the correlation of PROMs with ECOG PS and clinical outcomes in pancreatic cancer. Methods: We performed a retrospective analysis of patients with pancreatic cancer seen at the Henry Ford Health System between 09/2020 and7/2023, using ICD codes. The NIH’s validated and standardized Patient-Reported Outcomes Measurement Information System was used to capture 4 core domains: fatigue, pain interference, physical function, and depression. Patient-level variables and disease-specific variables were obtained by chart review from EHR. Kruskal-Wallis tests for continuous variables and or Fisher’s exact tests for categorial variables were used to compare the different ECOG scores and PROM scores and patient-level and disease-specific variables. Results: 176 patients were analyzed, with a median age of 65, 58% were male. Most patients had Stage 1 32.9% followed by Stage 4 25.9%, stage 3 22.9%, 1 32.9%. The majority had an ECOG score of 1, followed by, 0, 2, and only 10 had an ECOG PS of 3. There was no statistically significant difference in PS scores according to smoking status, race, or AJCC Stage but differed by age (P = 0.0007). PS score was not significantly associated with PROMscores on depression, fatigue, or pain interference. However, increasing PS scores were associated with a significant increase in low physical function PROM scores (P < 0.0001). Conclusions: Clinician-assessed PS is a single assessment of the patient’s tolerance to therapies subject to physician bias; our study provides encouraging data on the association between PS and patients’ reported physical function. The other PROM domains did not provide additional meaningful information on the patient’s function although are part of clinical decision-making. [Table: see text]
Implementation of patient navigation services to improve colorectal cancer health literacy in a vulnerable community health center population.
Authors: Brown Kari , Hartley Maria , Doreswamy Shriya , Mishra Sakshi , Ratnani Akshay , Behme Matthew
Published: June 2024

e23208

Background: Under-served community populations face social and health inequities which contribute to sub-optimal colorectal cancer (CRC) screening rates and excess mortality risk. Furthermore, these populations may not have the health literacy or food security necessary to mitigate the well-established nutrition-related risk of CRC. This quality improvement study aimed to improve CRC-related health literacy and dietary habits, with the additional goal of improving screening rates in our disadvantaged community health center population. Methods: This single-institutional study utilized the Plan-Do-Study-Act (PDSA) model to implement patient navigation services and administer a cross-sectional survey evaluating nutrition-related CRC risk. Patients eligible for screening were contacted by patient outreach coordinators prior to scheduled primary care appointments, and the survey was administered. During patient visits, outreach coordinators met with them to provide 1:1 education addressing CRC prevention, screening and nutrition. Information on free or low-cost fresh food options was provided to help address barriers such as food insecurity. The outreach coordinators also liaised with physicians to assist with coordination to services. Results: Prior to the intervention 58% of survey respondents (25/43) were not aware of any foods or dietary habits that decreased the risk of colorectal cancer; 51% (22/43) were not aware of foods that increased the risk of colorectal cancer. Most respondents (54%) were in fact not at all worried about possibly developing CRC in their lifetimes (22/41), while 34% (14/41) were a little worried, and the remainder (12%) very or extremely worried. 97% of respondents (33/34) felt more knowledgeable about CRC screening and felt more confident about improving their nutrition to reduce CRC risk after receiving the educational intervention, while 94% of respondents (31/33) stated they would subsequently make dietary changes. Conclusions: Health literacy regarding colorectal cancer was low in this underserved community population. Implementation of a patient navigation intervention led to increased knowledge and confidence in modifying dietary risk factors. However, preliminary data review did not reveal significant change in CRC screening rates during the initial phase of the intervention. One of the initially identified barriers included system-level delays in colonoscopy access. During the Act phase of the PDSA model, patient navigation services will be further optimized by workflow adaptation based on the response of outreach coordinators and patient-reported barriers regarding stool-based testing. [Table: see text]
Educating and empowering health care teams who present to the hospital to recognize and intervene on cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients on bispecific t-cell engager therapy (BiTEs): A quality improvement study.
Authors: Petrillo Alessandra , Seog Woo Jin , Halterman Justin , Winter Alex , Lee Christina Y.
Published: June 2024

e23212

Background: Treatment of oncologic disease with Bispecific T-Cell Engager antibodies (BiTEs) are an emerging novel immunotherapy with demonstrated efficacy in multiple hematologic malignancies. Notable side effects of BiTE therapy include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which can be life-threatening and must be rapidly identified. We aim to fill knowledge gaps surrounding CRS and ICANS for medical providers, particularly considering increased use of BiTE therapy. We hope that educating providers will allow faster recognition and treatment and will improve patient outcomes. Methods: Our study focused on the impact of educational presentations on awareness and identification of CRS/ICANS. Our intervention targeted the residents and attendings in the emergency department and the nurses, advanced practice providers, and hospitalists in the bone marrow transplant (BMT) unit at Stony Brook University Hospital. Anonymous surveys consisting of 9 multiple choice questions were conducted to assess baseline foundational knowledge of CRS/ICANS. QI consisted of a 15-minute educational presentation for both groups. The same surveys were repeated following the presentations to assess improvement in overall knowledge of CRS/ICANS. A two tailed independent T test was used to calculate significance. Results: The average pre-survey score for the emergency department (N = 37) was 39%. The average presurvey score for the BMT department (N = 13) was 45%. Significant improvements in scores after intervention were shown in both the emergency department (39% vs 66%, p = 0.0001) and the BMT department (45% vs 68%, p = 0.0006). Conclusions: Education among emergency department and hospitalist providers is essential in improving management of CRS and ICANS in patients treated with BiTEs. This quality improvement initiative confirmed a knowledge gap in CRS and ICANS amongst our healthcare teams. By providing educational resources to both departments, there was a significant improvement in this gap. Future directions for continued improvement in the detection and management of CRS/ICANS include patient medication identification cards, a central repository of treatment protocols, algorithms, and toxicities associated with BiTEs, and expanding our educational curriculum which are all currently under development at Stony Brook University Hospital.
Unveiling a low-hanging fruit: Single-center study on secondary immunodeficiency in newly diagnosed chronic lymphocytic leukemia and multiple myeloma.
Authors: Kharel Zeni , Kharel Himal , Mustafa S. Shahzad , Jamshed Saad
Published: June 2024

e23215

Background: Infectious complications are the leading cause of morbidity and mortality in patients with chronic lymphocytic leukemia(CLL) and multiple myeloma(MM). Despite recognized risks, evaluation of immune function occurs inconsistently. Our retrospective study evaluated practice patterns for assessing secondary immunodeficiency (SID) in newly diagnosed CLL and MM patients. Our aim is to identify areas for improvement to guide future prospective studies. Methods: We analyzed various immune parameters in newly diagnosed CLL and MM patients at Rochester Regional Health, Rochester, NY, focusing on the first six months of their clinical course, with descriptive data analysis. Results: Conclusions: Current infection prevention guidelines for newly diagnosed CLL and MM patients lack robust evidence. Despite our study’s inherent limitations (small, retrospective, single-center), based on our clinical experience, we propose the following recommendations: Complete SID assessment in all new diagnoses of CLL and MM, and this should include not only Ig levels but also vaccine response. If found to have abnormal SID evaluation, consider prophylactic antibiotics and Ig replacement, and consider reevaluation when appropriate to better define the duration of immunoparesis. Consider short-term Ig replacement (irrespective of IgG levels) and antibacterial prophylaxis for all newly diagnosed MM patients due to high infection risk during the initial six months. A thorough immune evaluation is non-invasive and low-cost, yet it can reveal clinically significant immune dysfunction, potentially influencing management in CLL and MM. Consequently, we hope our study will prompt the development of prospective, randomized studies to systematically evaluate these recommendations. [Table: see text]
Improving the understanding of integrative oncology approaches among hospitalized patients with cancer.
Authors: Luo Meiqi , Siddiqui Iqra , Flynn John , Khan Natalie , Monti Daniel , Bi Xia , Filicko-O'Hara Joanne E. , Gergis Usama , Porcu Pierluigi , Lopez Ana Maria
Published: June 2024

e23234

Background: Many integrative oncology (IO) outpatient (OP) cancer care approaches—yoga, acupuncture, massage, physical activity—have demonstrated benefit and are now part of guideline care. We report on a pilot inpatient (IP) IO consultative service aimed at introducing patients and families to IO at a time when cancer- and treatment-related symptoms can be significant. As a measure of patient-centered care, we assessed patient’s change in perceived understanding, intention to promote health, confidence in care, and plan for IO OP follow up. Methods: IO consultations that assess nutrition, activity, and stress were made available to patients in the Bone Marrow Transplant Unit at Thomas Jefferson University Hospital (TJUH) starting in July 2023 as ordered by the primary oncology team. Consultations (69) have been conducted by an Integrative Medicine Fellow and an attending Board Certified in both Medical Oncology and Integrative Medicine. The post-IO consultation survey includes 7 questions with a 5-point Likert Scale (1 = Do Not Agree, 5 = Completely Agree).The survey was initially offered as an online link. A paper format was developed at patient request. Results: A total of 34 patients (50%) completed the post-consultation survey. Conclusions: Patients expressed a greater likelihood of focusing on wellness through diet, nutrition, meditation, and stress reduction (76.4%) and of taking steps to promote their health (87.9%); as well as an improved understanding of the relationship between nutrition and health (88.2%) and stress and health (88.2%). Patients noted a more positive view of TJUH (84.4%) and greater confidence in their treatment (81.8%). In addition, only 10% of patients decided not to pursue an IO appointment after discharge. These pilot data suggest a benefit to IP IO consultation. [Table: see text]
Mobilizing exercise recommendations for people with bone metastases: An experience-based co-design approach.
Authors: Nadler Michelle B. , Bland Kelcey , Neil-Sztramko Sarah , Langelier David , Lane Kirstin N. , Chalmers Alana , Dinardo Rhonda , Alibhai Shabbir M.H. , Capozzi Lauren , McDonald Karen , Copp Jane , Mackenzie Kelly , McNeely Margaret , Lambert Leah , Bates Alan , Simmons Christine E. , Campbell Kristin L.
Published: June 2024

e23241

Background: People with bone metastases have historically been advised to limit exercise due to potential risks, such as fractures. Although published exercise recommendations by the International Bone Metastases Exercise Working Group emphasize regular exercise may benefit people with bone metastases, adopting guidelines into clinical practice remains challenging. Our study aims to use an experience-based co-design (EBCD) approach to collaborate with knowledge users (KUs) to develop knowledge mobilization (KM) products and a dissemination plan to promote the adoption of exercise recommendations for people with bone metastases. Methods: Three KU groups participated in EBCD: patient/family partners, oncology healthcare providers (e.g., physicians, nurses, allied health), and community-based exercise professionals (e.g., physiotherapists, exercise physiologists). Through four facilitated meetings, KM products were co-created and a dissemination strategy was planned. A survey of exercise professionals was used to collect further information on professional development (PD) preferences. Results: Twenty-nine KUs from five Canadian provinces participated (n = 10 patient/family partners, n = 9 healthcare providers, and n = 10 exercise professionals). KM products prioritized for co-development were: 1) a patient education handout; 2) patient education videos; 3) a clinical communication tool; and 4) PD resources for exercise professionals and healthcare providers. Finalized KM products will be presented at the meeting. A total of 183 international exercise professionals completed the PD survey, with 80% indicating that more PD resources were needed for bone metastases, focusing on exercise safety, feasibility, and prescription considerations. The dissemination plan will involve partnerships with Canadian and international organizations. Conclusions: Collaborating with KUs through EBCD may enhance KM product development and maximize utility and acceptability compared to researcher-designed products. Our KM products, tailored to support people with bone metastases to exercise safely, may also increase healthcare providers' and exercise professionals' satisfaction by improving the quality of information they can offer patients. A fulsome evaluation is planned to assess the reach, use, and partnership indicators of the KM products and dissemination plan.
Treatment patterns and outcomes in patients with early onset cholangiocarcinoma: A large database analysis.
Authors: Grewal Udhayvir Singh , Manchkanti Srija , Fei Naomi , Chandrasekharan Chandrikha
Published: June 2024

e23294

Background: Although the average age of onset of cholangiocarcinoma (CCA) is ≥ 65 years, recent data have demonstrated an alarming rise in incidence of CCA in the United States (US) among people younger than 50 years of age. However, robust data regarding the characteristics and outcomes of CCA among young patients are lacking. Methods: We used TriNetX, a national database comprising approximately 74 million patients across 54 healthcare organizations in the US, to perform the current analysis. We retrospectively identified patients with CCA (using ICD-10 code C22.1) from Jul 2009 to Jan 2022. We then performed comparative analysis between patients ≤ 49 years (early-onset CCA or EOCCA) and ≥ 50 years old (average-onset CCA or AOCCA). We performed a comparative analysis of baseline characteristics, treatment patterns and overall outcomes. We used the Chi-square test for the comparative analysis and Kaplan-Meier estimates were plotted for survival analysis. A p-value of < 0.05 was considered statistically significant. Results: We included a total of 1,343 patients with EOCCA. Compared to AOCCA, patients in the EOCCA group were more likely to be females (51% vs 48%, p < 0.0001), African Americans (13% vs 9%, p < 0.0001) and have a history of primary sclerosing cholangitis (7% vs 1%, p < 0.0001). Patients in the EOCCA group were more likely to undergo surgical resection (9.7% vs 8%, p = 0.007), liver transplant (4.5% vs 1.6%, p < 0.0001) and adjuvant chemotherapy (39.2% vs 33.5%, p < 0.0001). Young patients were also more like to receive palliative chemotherapy (16.7% vs 12.6%, P < 0.00001) and FGFR-directed targeted therapy (1.5% vs 0.3%, p < 0.00001). Compared to older patients, we noted a significantly higher overall survival among young patients undergoing surgical resection (85 months vs 43 months, p = 0.008) and patients with advanced disease (28 months vs 15 months, p < 0.0001), however, no difference in overall survival was noted between young and older patients undergoing liver transplant (88 months vs 117 months, p = 0.6). Conclusions: We present a large real-world analysis highlighting treatment patterns and outcomes in patients with EOCCA. Young patients received more surgical resections, both adjuvant therapies and palliative therapies, and had a significantly longer overall survival than their older counterparts. Although more patients underwent liver transplant in the EOCCA group, post-transplant survival was not significantly better compared to their older counterparts. Prospective clinical studies tailored to assess surgical and systemic therapeutic approaches specific to EOCCA patients are warranted.
Evaluation of cyclin-dependent kinase 4/6 inhibitor-induced serum creatinine elevations in patients with hormone receptor positive breast cancer.
Authors: Ly Emily , Howard Frederick Matthew , Chen Nan , Hahn Olwen Mary , Fleming Gini F. , Nanda Rita , Patel Shivani , Thimothy Lida , Yang Heng
Published: June 2024

e23304

Background: Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have improved the efficacy of endocrine therapy in hormone receptor-positive (HR+)/HER2- breast cancer (BC) and are now used in both early-stage and metastatic disease. In the MONARCH-3 trial, 98% of patients (pts) treated with abemaciclib (abema) experienced elevated serum creatinine (sCr). Chappell et al. reported that abema caused pseudo-elevation in sCr by inhibiting renal tubular secretion. This effect was not evaluated in trials of palbociclib (palbo) and ribociclib (ribo), but case reports suggest that pseudo-sCr elevations are likely a class effect of CDK 4/6i. In this retrospective study, we sought to evaluate the incidence of sCr elevation in pts being treated with CDK4/6i for early and advanced stage BC. Methods: This single-center retrospective analysis included pts aged ≥18 years who received at least one dose of palbo, ribo, or abema for the treatment (tx) of HR+/HER2- BC in the early or advanced setting at the University of Chicago Medicine from January 2015 to August 2023. Pts were categorized into subgroups based on the CDK4/6i received. The primary objective was to evaluate the incidence of pseudo-sCr elevation in the subgroups. sCr elevation was graded according to Common Terminology Criteria for Adverse Events Version 5. CDK4/6i-induced pseudo-sCr elevation was suspected when the sCr elevation could not be fully explained by other causes. Secondary endpoints included the grade, onset, duration, and clinical consequences of pseudo-sCr elevation. Incidence of pseudo-sCr elevation among the three groups were compared using the Chi-squared test. Descriptive statistics were used for pt characteristics and secondary endpoints. Results: In total, 143 pts were analyzed. Pseudo-sCr elevation was suspected in pts treated with palbo, ribo, and abema, with incidences of 16% (8/50), 14% (6/43), and 20% (10/50), respectively. Rates did not significantly differ between agents (p = 0.727). Among pts with CDK4/6i-induced pseudo-sCr elevation, all pts experienced either grade 1 (8.3%) or 2 (91.7%) events, with a median sCr increase from baseline to peak of 0.69 mg/dL (range, 0.39 – 2.9 mg/dL). The median onset from tx initiation to first sCr elevation was 33.5, 42, and 21.5 days, for palbo, ribo, and abema, respectively. Based on available data at study cutoff, 13 of the 24 pts with suspected pseudo-sCr elevation were still on tx with continued sCr elevation. Nine of 24 pts were no longer on CDK4/6i tx; none due to sCr elevation. Three of the 9 pts had sCr returned to baseline within 3 months of tx discontinuation. Conclusions: Pseudo-sCr elevation appears to be a class effect of CDK4/6i, with similar rates of sCr elevation observed across the three CDK4/6i currently FDA approved. Further analyses evaluating differences by age, race, and stage are ongoing.
Clinical and outcome patterns in epithelial ovarian cancer (EOC) within a Latin American cohort.
Authors: Roque Katia , Heredia Marcos , Ruiz Rossana , Galvez-Nino Marco , Castro-Mollo Melanie Wendy , Flores Claudio J. , Coanqui Ofelia , Valdiviezo Natalia , Olivera Hurtado de Mendoza Mivael , De Mello Ramon Andrade B. , Mas Luis
Published: June 2024

e23308

Background: Epithelial Ovarian Cancer (EOC) is an heterogenous disease which is usually diagnosed inadvanced stages. Despite the advent of new therapies, the outcomes for this disease remain poor in certain scenarios. We describe the clinical features and survival outcomes in a developing country. Methods: Retrospective study based on case review of women with newly diagnosed EOC between 2015 and 2017 at Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima- Peru. Descriptive analysis was conducted for clinical characteristics, epidemiological factors and treatment. PFS was calculated from the date of diagnosis until the first documented progression and OS from the date of diagnosis to death. Both were calculated using the Kaplan Meier curve. Results: 234 patients were included, the most common histology subtype was high grade serous carcinoma (47,5%), followed by mucinous (15.9%) and clear cell carcinoma (15.4%). Median age was 55.7 yo (range 19-88). Breast and ovarian cancer family history were reported in 3.8% and 3.0%, respectively. 35.8% of patients were overweight, and 12.5% were obese. Most patients (61.5%) were diagnosed at advanced disease (III-IV) and the most common site of metastasis was liver (43.6%) and lung/pleural (28.2%). BCRA testing was performed only in 6% of patients, and 4/14 patients had a pathologic mutation. Ca125 was elevated in 86.2% of patients. Regarding treatment, all patients with early stage disease (I-II) underwent surgical staging. For advanced stage disease, 47.6% (69/145) of patients underwent upfront surgery and 41.4% (60/145) received platinum-based chemotherapy in neoadjuvant setting; 57.3% (35/61) of these patients achieved optimal secondary cytoreduction. With a median follow up of 74,4 months, median PFS was 32.61 months (0.6-474) and global median OS was 58.13 months. Median OS for early disease (I-II) was not reached and for advanced disease (III-IV) was 33.73 months. Survival rate at 5y for all stages was 45.2%; 60.8% and 28.4% for early and advanced disease, respectively. Conclusions: These findings highlight the prevalence of high-grade serous carcinoma and the significance of advanced-stage diagnosis in the survival outcomes. In the era of targeted therapies, the lack of access to BRCA detection tests restricts therapeutic options and, consequently, hinders responses in this group of patients.
Prevalence of polypharmacy, drug-drug interactions, and inappropriate prescription in elderly patients with urological cancers.
Authors: Castro Carballeira Clara , Ibañez Alda María , Lanza María , Sánchez Laura , Sotelo Marta , Cacho Diego , Gómez Borja , Duran Ignacio
Published: June 2024

e23312

Background: Around 50% of new cancer diagnoses occur in patients (pts) > 65 years. Older adults tend to have more comorbidities and therefore prescription of several drugs. Polypharmacy (PP) [defined as prescription of > 5 drugs] has been identified as a prognostic factor and might also lead to relevant drug-drug interactions (DDI) and it is also associated in occasions with inappropriate prescriptions (IP). This study aims to determine prevalence of PP, DDI and potential IP in a uro-oncology clinic. Methods: Pts ≥ 70 years with urological tumors consecutively seen in a medical oncology clinic [May 1st- August31st2023] were offered to complete a questionnaire that included questions about drugs regularly taken, doses, frequency, objective of the treatment along with some key epidemiological data. A descriptive analysis of this information was performed to identify PF along with a search for DDI ( DrugDex ®) and IP (STAR/STOPP criteria). Results: 91 pts agreed to participate and 87 complete the questionnaires. Mean age was 76 years (range 70-91) and 84.5% were men; 64%, 31 and 5% had ECOG 0,1 and 2 respectively. The predominant cancer type was bladder (41%), followed by prostate (40%) and kidney cancer (19%). Polypharmacy was identified in 54 pts (62%), with 12 pts (22%) having ≥ 10 drugs prescribed. Two cases (2%) of duplicity of treatment were found (laxative; hypnotic). Ninety-five major and 37 moderate DDI were detected, of which 8 occurred between anticancer drugs (abiraterone, pazopanib, everolimus and carboplatin) and outpatient treatments. An IP analysis is being currently conducted and data will be presented at the meeting. Conclusions: Our study shows a high prevalence of polypharmacy in older adults with urological tumors and a significant rate of drug-drug interactions including interferences with oncological treatments. These results highlight the need for careful reviewing and monitoring the drugs prescribed to our patients in the clinic and calls for strengthen collaborations with pharmacists and nurses to optimize integral management of GU cancer patients.
Melanoma immunotherapy longitudinal database: A comprehensive approach to capture oncological and toxicity data.
Authors: Abdel-Wahab Reham , Zuri Qais , Rinsurongkawong Waree , Pappachan Binu , Swaim Michael , Master Priya , Harris Calvin , Lewis Jeff , Abdel-Wahab Noha , Diab Adi
Published: June 2024

e23314

Background: Evaluating immunotherapy approaches is consistently performed in melanoma, a forefront cancer in immunotherapy responsiveness. Although immune checkpoint inhibitors (ICIs) showed the highest significant survival benefits in melanoma, 50% of patients experience recurrence/refractory disease, and ~59% develop grade 3/4 immune-related adverse events (irAEs). Thus, understanding the disease's natural history, exploring biomarkers of response/toxicity, and identifying the efficacy/safety of immunotherapy using real-world data is warranted. Methods: We established a centralized pro-/retrospective database on Research Electronic Data Capture (REDCap), encompassing patients' demographics/comorbidities, disease risk factors, clinicopathological parameters, genomic/immune profiling, treatment modalities, tumor outcomes, irAEs, and patients’ reported outcomes (PROs). Additionally, to streamline data collection and minimize the required time, effort, and cost for manual retrieval, we developed an automated pathway for data capture using MD Anderson Cancer Center (MDACC) electronic data capture (EDC) tools which pull clinical data from EPIC. Data quality will be validated by comparing it to manually retrieved data from an ongoing study of melanoma patients treated with ICIs in the adjuvant setting (NCT04990726). Results: A total of 4074 immunotherapy-treated melanoma patients were identified. We automatically captured demographics and laboratory values at predefined time points from REDCap, along with PROs using validated electronic self-reported questionnaires already built in REDCap. We also automatically captured family history, comorbidities, pathology data, and cancer treatments from the Data Management Initiative (DMI) validated software that automatically captures data from 12 various institutional sources that complement each other, including Radiation Oncology Database, the Biospecimen Information Management System,...etc. Moreover, genomic data were automatically pulled from the Molecular and Clinical Data Integration Platform for 1850 patients. Automated capture of tumor response and irAEs according to the Response Evaluation Criteria in Solid Tumors 1.1. and Common Terminology Criteria for Adverse Events version-5, respectively are currently ongoing and will be presented. Conclusions: Integrating EDC tools demonstrated accurate real-time data capture and minimized the manual retrieval burden. Our immunotherapy-treated melanoma patients’ cohort provides a comprehensive and a valuable resource for exploring the safety signals and efficacy of various immunotherapeutic approaches beyond clinical trials.
Physician justification for anti-cancer treatment decisions in the evolving oncology market.
Authors: Moseley Angelena , Brierly Margaret
Published: June 2024

e23317

Background: Oncology is a rapidly expanding pharmaceutical space, driven by innovative research and clinical technology. Continued growth in anti-cancer therapy has generated an exceedingly competitive market. As treatment options increase, physicians must weigh a variety of factors to make individualized care decisions. Many elements are patient-specific, but physician biases may also impact selection. As the market evolves, it is unknown whether oncology providers will shift priorities to align with contemporary findings or continue to trust in historical experiences. Methods: The Ipsos Global Oncology Monitor is an online, multi-center medical chart review of oncology patients receiving drug therapy. Over 1,900 cancer-treating physicians in the United States were screened for seniority and caseload and submitted data on 253,051 cancer patients (aggregate; all tumor types) between January 2020 to December 2023. Upon record submission, physicians were prompted to select up to three responses most associated with the reason for prescribing the reported therapy. Responses were chosen from a finite list of closed-ended options. Results: Influence of “Approved Standard of Care” fell amongst sampled physicians, cited as a reason for selecting treatment in 61% of reported annual patients in 2023, declining by 2.94 percentage points since 2020. “Biomarker results” recorded increased influence on therapy selection, rising in association with 8% of reported patients in 2020 to 11% in 2023. Within tumor-specific cohorts, “Maintain/improve quality of life” was a notable reason for drug therapy decisions in both breast and colorectal cancer patient subsets in 2023 (10% and 19% respectively). Contrary to the overall patient cohort, drug therapy choice for reported prostate cancer patients has increasingly shown association with “Approved Standard of Care” (53% in 2020 to 60% in 2023). Conclusions: Results of this study highlight the evolution of factors influencing anti-cancer treatment decisions in sampled physicians. Sampled providers appear to be shifting away from universal treatments, as shown by lowered association with “Approved Standard of Care”. Sampled physicians seem to be opting for specific therapies, demonstrated by rising influence of “Biomarker results”. Discrepancies between tumors merit expansion of research in rarer indications and emphasize the importance of diagnostic testing to continue improving quality of care. Further investigation using comparator cohort is warranted.
Unveiling the impact: Exploring thrombotic outcomes in hospitalized patients with COVID-19—Comparing those with and without a cancer diagnosis.
Authors: Bhinder Muhammad Mujtaba , Davis Elaine A. , Welch Christine A. , Kamran Amir Shahzad
Published: June 2024

e23318

Background: There is a shared hypercoagulable association of COVID-19 and cancer, noting an increased risk of thromboembolic events (TEE)in both conditions. The current study focuses on patients with concurrent COVID-19 and underlying cancer and compares incidence of TEE and related outcomes in this complex intersection of acute viral infection and oncological challenges. Methods: In this retrospective cohort study, we examined data from the Charleston Area Medical Center’s (CAMC) COVID-19 Registry, involving 5,479 adult, symptomatic, PCR-positive COVID-19 hospitalized patients (3/1/2020 to 1/20/2024). Demographics, co-morbidities, lab values, treatments, and outcomes were assessed. Propensity score matching (3:1) non-cancer patients vs those with an active cancer diagnosis was undertaken using sex and age. SAS 9.4 was utilized for the analysis. The groups were compared using Chi-square/Fisher’s Exact tests for categorical variables and t-tests for continuous variables and a logistic regression modelling to determine differences in key variables, the incidence of thromboembolic events and other outcomes. Results: After propensity matching, 1,623 non-cancer and 427 active cancer patients were included. The incidence of venous thromboembolism (VTE) was higher in the active cancer group (9.42% vs 4.2%, P < 0.001) with no significant differences in acute stroke. Intensive care unit (ICU) admissions, mechanical or non-invasive ventilation requirement, and mortality were not different although more patients with cancer were discharged to hospice (11.8% vs 3.3%, P < 0.001). However, mean D-dimer results in both groups were > 2.5 mg/L, it was not performed consistently. The active cancer group had greater frequencies of abnormal ferritin levels (59.1% vs 49.1%, P=0.01), and elevated procalcitonin levels > 0.05 ng/mL (72.9% vs 60.6%, p < 0.001). Among key treatments, remdesivir was used more frequently in cancer patients (41.4% vs 35.7%, P < 0.01). In addition to the cancer diagnosis (OR = 1.729 95% CI [1.1-2.8] P =0.02), LOS > / = 7days was also a predictor of TEE (OR= 1.825 95% CI [1.1-2.9] P < 0.01). Conclusions: Symptomatic VTE rates in our COVID-19 and active cancer cohort align with published studies. Diligence in evaluation of D-dimer, early detection of TEE and adherence to published guidelines in prophylaxis and treatment is recommended.
Evaluating hemoglobin thresholds for blood transfusions in oncology patients admitted in the intensive care unit.
Authors: Boban Abijha Biju , Strike Andrew , Patel Dhaval , Rynarzewska Ania
Published: June 2024

e23319

Background: Current guidelines recommend transfusing at a hemoglobin (Hb) threshold of 7g/dl. There is a lack of evidence to support a specific threshold for transfusion in patients with active malignancy admitted to the Intensive Care Unit (ICU). This study attempts to determine an evidence-based threshold for blood transfusions in cancer. Methods: A retrospective study was done to study 561 patients with an active cancer diagnosis admitted to Northeast Georgia Medical Center ICU between 2017 and 2023 that received at least one unit of blood transfusion. Chi-Square test of association with Bonferoni correction was applied to the top five common cancers seen in ICU: Leukemia, Lymphoma, Brain tumors, Lung cancers, and GI cancers. It compared three thresholds of transfusion and looked for any change in mortality risk, readmissions, need for multiple transfusions, prevalence of new onset or recurrent heart failure, development of altered mental status, or cardiac arrest. The three thresholds for transfusions that were studied were < 7g/dL, < 8 g/dL, and > 8 g/dL. The studied cancer types were further divided into either hematologic or solid tumors. Results: There was a decrease in overall cancer readmissions compared to expected over 30 days by 64%, 60 days by 44%, and 90 days by 47.5% when transfused for a Hb threshold of <8 g/dL compared to an increase of 22.8%, 18.2%, and 18.8% in 30-, 60-, and 90-day readmissions when transfused for a Hb threshold of <7 g/dL. When divided by cancer types, there was a significant decrease from expected by 30%, 47.5%, and 56% in 30-, 60-, and 90-day readmissions for patients with solid tumors for a Hb threshold of < 8 g/dL. Mortality risk decreased by 50% and the need for multiple transfusions decreased by 21% when transfused for a Hb threshold of < 8 g/dl. Of note, there was no significant association between transfusion levels and associated reactions. There was a decrease of 82% in altered mental status when transfused for threshold of Hb <8 g/dL. Finally, significant association was not found with AKI, cardiac arrest, or heart failure and any Hb transfusion thresholds. Conclusions: Based on these results, there is a significant mortality benefit and decreased length of stay for cancer patients admitted to ICU when blood transfusion is undertaken at a hemoglobin threshold of <8g/dL. These results should be further investigated in a randomized controlled trial.
Comparison of drug treatment intent in stage IV solid tumors in EU4+UK.
Authors: Gallo Federico , Ng Elsa
Published: June 2024

e23323

Background: The goal of cancer treatment may vary based on multiple factors. This study uses real-world data to compare treatment intent, and its evolution over time among patients with solid tumors; whilst we focus on stage IV cohorts, a comparison vs. stage I-III patients is also made, for context. Methods: Ipsos’ Global Oncology Monitor is a multi-stakeholder, physician-reported syndicated patient record database. 3,308 solid tumor-treating physicians (France = 834, Germany = 709, Italy = 578, Spain = 626, UK = 561) were screened for seniority and caseload and submitted data on 329,154 patients (France = 64,985, Germany = 77,709, Italy = 64,507, Spain = 65,427, UK = 56,526). Data were collected online from January 2020 to September 2023. Sample data were projected to the wider clinical population using market sizing extrapolations. Results: Of all solid tumor patients reported, regardless of stage, control cancer spread and/or growth (extend life) is the most common cited goal by sampled physicians when choosing drug therapy for the patient in question (average ~50% reported patients). This is followed by intent of eliminating cancer cells to undetectable levels (curative), while the intent to ease cancer symptoms (palliative) is typically less likely to be selected. Treatment intent at stage I-III showed similar trends, with curative being the most common goal (average ~70% of reported patients). When focusing on Stage IV solid tumors we observe life extension generally emerging as the main intention; a more nuanced analysis reveals similarity between Germany and Spain, where palliative intent is cited more often by sampled physicians compare to other regional counterparts. These differences are shown in Table 1. Little change seen in curative intent from 2020 to 2023 across all regions, except UK, where a downward trend is reflected from Q3 2022 onwards with a concurrent increase in extend life. Conclusions: This study indicates that treating to cure is a common aim for EU4+UK sampled physicians when giving drug therapy to stage I-III solid tumor patients, whilst extending life is the notable goal when considering stage IV patients. Additional analysis of tumor- and region-specific changes over time may help establish any potential influences on drug treatment choice due to factors such as reimbursement and treatment type availability. Further investigation using comparator cohort is warranted. [Table: see text]
Chalazion associated with proteasome inhibitors approved for multiple myeloma: Analysis of FAERS database.
Authors: Singh Harkarandeep , Kaur Uttamjot , Neupane Niraj , Saeed Hassan , Kharel Himal , Gill Prabhsimrat , Shrestha Asis
Published: June 2024

e23325

Background: Proteasome inhibitors (PI) are a class of drugs used in the treatment of Multiple Myeloma. The FDA has approved three PIs for this indication (Bortezomib, Carfilzomib, and Ixazomib). Various studies, and case reports have described the occurrence of chalazion with Bortezomib use and subsequent discontinuation of therapy but it’s association with other PIs from the class remains poorly understood. Methods: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System database to analyze the strength of association of chalazion with Bortezomib, and with other Proteasome Inhibitors in patients above 18 years of age. We employed disproportionality signal analysis and calculated the reporting odds ratio with a 95% confidence interval. Results: Within the FAERS database, a total of 78,596 adverse events were reported with the use of the three FDA approved PIs in adults, out of which chalazion accounted for 56 cases. Most of the cases were reported with Bortezomib use (54 cases), followed by Carfilzomib (2 cases), and Ixazomib (1 case). In cases with mention of sex, and age, 64.7% were in females, and 35.3% in male patients, whereas 47% patients were within the age group of 18-64, and 53% being above 64 years of age. While most of the cases had non-serious outcomes, death was reported in 2 cases, and hospitalization was needed for 5 cases. Only Bortezomib was associated with a significantly positive signal strength (ROR 32.9, 95% CI 25.1-43.1, Chi-squared Yates 1596.27). Conclusions: The study offers the largest retrospective review of association of chalazion with proteasome inhibitors. It is most strongly associated with Bortezomib use, and females are twice as likely to develop it as compared to males. Elderly patients also seem to be at a slightly higher risk. Overall, chalazion seems to account for only a small number of side effects reported with proteasome inhibitors, and a majority of cases have non-serious outcomes.
Understanding clonal heterogeneity and mechanisms of methotrexate resistance in two osteosarcoma PDX models.
Authors: Jusu Sylvester , Longo-Sorbello Giuseppe S. A. , Zhongting Zhang , Zhaohui Xu , Roth Michael , Harrison Douglas James , Gill Jonathan Benjamin , Gorlick Richard Greg
Published: June 2024

e23512

Background: Osteosarcoma is a primary malignant bone tumor that is known to have significant intratumoral heterogeneity with branched cancer evolution. The lung is the most frequent site of metastatic disease and relapse occurs in more than 30 % children and young adults. It has been revealed that the metastatic ability and resistance of cancers including osteosarcoma might be due to the presence of a subset of cells within the intra-tumorally heterogeneous population. We investigated the emergence of resistant clonal subpopulations following targeted methotrexate treatment in two patient derived xenograft (PDX) models in vitro and in vivo. Our aim was to not only track the subclonal population of cells that establish in the lungs but also to identify clonal drivers and the mutational signature of the genes and pathways involved in MTX resistance. Methods: We previously established 20 barcoded osteosarcoma PDX models and demonstrated that the application of methotrexate (MTX-IC95) treatment as a selective pressure in seven models produces clonal subpopulations that were more resistant to MTX. In the current work we used barcoded next generation and RNA sequencing techniques to map the clonal and transcriptomic architecture of MTX resistant single clones in M36 and OS252 PDX models. We next injected the barcoded PDX cells intratibially in twenty severe combined immunodeficiency disease (SCID) mice to track the clonal population/subpopulation of cells that metastasize to the lungs. Following primary tumor growth, limb amputation was carried out and mice were treated with methotrexate or vehicle for two weeks. Primary tumor, blood and lung samples were collected after death from metastasis or euthanasia. All samples collected were snap frozen in liquid nitrogen and stored at -800C. DNA and RNA was extracted and analyzed by PCR, NGS or WES to map clonality, mutational and evolutionary profiles. Results: MTX treated single clones showed diversity and barcode abundance when compared to vehicle; barcode abundance reduced in the resistant clonal subpopulations when compared to the vehicles. Ten unique subclones were shared in both vehicle and MTX resistant clones in M36 while OS252 had only one shared subclone respectively. More than 50% of the injected mice developed primary tumors and matched lung micrometastases. We are currently analyzing both targeted and RNA sequencing results to further understand clonality, the mutational signature of the genes (DHFR, MTR, FPGS, GGH) and pathways involved in MTX resistance. Conclusions: We investigated mechanism of methotrexate resistance in two barcoded PDX models in vitro and in vivo using cytotoxicity, next generation and RNA sequencing techniques. Targeted amplicon sequencing of key genes involved in antifolate pathway will yield new information on clonal evolution and mechanisms of resistance.
Correlation between imatinib trough concentration and efficacy in patients with advanced GIST with different genotypes.
Authors: Xia Yanzhe , Zhang Xinhua , Jiang Aiting , Guo Xiaodan , Lin Jiahui , Huang Shaoqing , Cai Shirong , He Yulong , Tang Ke-Jing
Published: June 2024

e23515

Background: Imatinib (IM) has significantly enhanced the prognosis of patients (pts) with advanced gastrointestinal stromal tumors (GISTs). The clinical outcomes may correlate with IM exposure. However, the efficacy threshold, particularly based on different primary KIT mutant, remains undefined. This study aimed to establish the efficacy threshold of IM plasma trough concentration (Cmin) at steady-state in Chinese pts with advanced GIST, additionally to define subgroup thresholds based on various primary KIT mutations. Methods: This was a single-center, prospective, observational cohort study. Pts with histologically confirmed recurrent/metastatic GIST who received regular IM treatment and had undergone at least two measurements of steady-state IM Cmin were enrolled from Jul 2017 to Jun 2022. Clinical outcomes including objective response rate (ORR), survival, and IM Cmin were assessed. Results: A total of 168 pts with a median age of 52y were enrolled. The primary lesion locations comprised stomach, small intestine, rectum and others. Metastatic lesions were found in the liver, peritoneum, both liver and peritoneum and others. Median sum of longest diameter of target lesions was 10.7cm. Of 168 pts, 117 (69.6%) harbored KIT 11, 27 (16.1%) harbored KIT 9, 5 (3.0%) harbored PDGFRA, and 9 (5.4%) were KIT/PDGFRA wild type. During IM response period, 104 pts combined with surgical treatment (surgery or interventional therapy). After a median follow-up duration was 50.6m (range, 16.3–189.8), 72 pts had disease progression and 20 died. Estimated median progression-free survival (mPFS) for all patients was 79.4m (95%CI 55.7–103.1). The median overall survival was not reached. A Cmin threshold of ≥738ng/ml defined by log-rank test was associated with longer PFS for the whole population (P = 0.002) irrespective of other clinical characteristics. Pts with an IM Cmin below 738ng/ml exhibited a shorter mPFS (25.3m, 95%CI 41.9–97.1) compared to those surpassing this threshold (96.7m, 95%CI 65.8–127.6). The ORR for the whole population was 73.0% (CR 2.2%, PR 70.8%), with no significant difference observed between pts with IM Cmin below and above 738ng/ml. For pts with KIT 11 and KIT 9 mutations, the efficacy thresholds for IM Cmin were ≥680ng/ml and ≥1877ng/ml, respectively. Multivariate Cox regression analysis revealed that IM Cmin ≥738ng/ml, primary gastric origin, liver-only metastasis, sum of target lesions diameter ≤5cm, KIT 11 mutation, and combined with surgical treatment were favorable prognostic factors. Conclusions: IM exposure significantly correlates with clinical benefits in advanced GISTs, with an IM Cmin above 738ng/ml associated with a longer PFS in Chinese population. Considering different primary KIT mutant, a threshold of 680 ng/ml could be considered for efficacy in KIT 11 mutations, while a higher Cmin of 1877 ng/ml was necessary for KIT 9 mutation.