bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management impact of preoperative germline genetic testing in patients with breast cancer at the Lifespan Cancer Institute.
Authors: Lew Kaitlyn P. , Dizon Don S. , Phornphutkul Chanika , Benson Cindy , Wiggins Doreen Leyden , Fenton Mary Anne Anne , Taneja Charu , Massingham Lauren J. 
Published: June 2021

10523 Background: Breast cancer is a heterogenous disease and management is complex. Advances in next generation sequencing has allowed genetic testing to be more accessible. However, conveying results to patients and care team can be challenging due to various variant classifications. Diagnostic results have the potential to guide management. Nondiagnostic results can be misinterpreted. The extent to which preoperative genetic testing affects management of newly diagnosed breast cancer is unknown. Methods: Newly diagnosed breast cancer patients were identified via review of breast tumor board between May 2019 and March 2019 followed by chart review to collect detailed information. Results: 408 newly diagnosed breast cancer cases were queried. Genetic evaluation was recommended and completed in 68%, not recommended (did not meet NCCN criteria) in 30% and declined in 2.7%. The genetic evaluation recommended cohort was associated with a higher mastectomy rate in comparison with when not recommended (31% vs. 9%, p=0.0001). Of those who completed genetic testing: 12% harbored a pathogenic/likely pathogenic variant (PV/LPV), 26% had a nondiagnostic variant of uncertain significance (VUS) and 61% had negative testing. Comparison between nondiagnostic test results (negative and VUS) and diagnostic test results revealed significantly increased number of women in the diagnostic group who chose mastectomy over breast conservation therapy (BCT, nondiagnostic 20% vs diagnostic 39%, p=0.018). When negative, VUS, and PV/LPV were each independently analyzed, diagnostic test results again revealed a significantly increased number of mastectomies over BCT (p<0.05). Comparison of surgical choices in nondiagnostic VUS vs. negative results was not significantly different (Table). Comparing the surgical timelines, completing a genetic evaluation did not affect surgery timing (mean 2.3 vs. 2.2 months, p>0.5). Conclusions: Germline genetic testing in patients with newly diagnosed breast cancer impacts clinical management. Those harboring a diagnostic result were more likely to choose mastectomy over BCT. Not surprisingly, mastectomy rate was higher among those where genetic evaluation was recommended, possibly due to concerning personal or family history. The mastectomy rate was higher among those with a diagnostic result, indicating an understanding of the genetic testing significance by patients and the care team. More importantly, those who harbored nondiagnostic VUS did not make significantly different surgical choices compared with negative genetic testing, highlighting the critical role of proper genetic counseling and being part of the care team. We conclude consideration of genetic evaluation is clinically useful and feasible without affecting the surgical timeline.[Table: see text]
The impact of radiological assessment schedules on progression-free survival in metastatic breast cancer: A systemic review and meta-analysis.
Authors: Dabush Dor Reuven , Shepshelovich Daniel , Shochat Tzippy , Amir Eitan , Tibau Ariadna , Goldvaser Hadar 
Published: June 2021

1086 Background: The impact of the interval of radiological assessment on the magnitude of benefit observed in randomized trials (RCTs) in metastatic breast cancer is undefined. Methods: All RCTs investigating anti-neoplastic drugs for metastatic breast cancer published between 2006 and 2019 were identified. Intervals for restaging were categorized as short ( < 9 weeks) or long (≥9 weeks). Hazard ratios (HRs) and 95% confidence intervals for progression-free survival (PFS) and overall-survival (OS) were pooled in a meta-analysis and compared between trials employing short and long restaging intervals assessed as subgroup analyses. Analyses were repeated for pre-specified subgroups according to disease subtype, drug type, whether experimental therapy was added to or replaced standard treatment and whether HR for PFS was < 1 or ≥1. Results: Eighty-nine studies comprising 95 comparisons and 44,901 patients were included. The magnitude of PFS benefit was non-significantly larger in trials which employed short compared to long restaging intervals (HR 0.79 vs. 0.86, p = 0.15). Short restaging interval was associated with significantly higher magnitude of effect on PFS in pre-specified subgroups including non-first line studies (HR 0.78 vs. 0.92, p = 0.04), studies with drugs replacing standard treatment (HR 0.86 vs. 1.04, p = 0.02) and studies performed exclusively in human epidermal growth factor receptor 2 (HER2) positive disease (HR 0.72 vs. 0.90, p = 0.02). Restaging interval was not associated with OS for all included studies (HR 0.92 vs. 0.93, p = 0.66) or for any of the pre-specified subgroups. Conclusions: Shorter restaging intervals are associated with a higher magnitude of effect of PFS, but not OS. Awareness of the impact of the restaging interval on quantification of intermediate endpoints such as PFS is important for the design and interpretation of RCTs.
Association between baseline geriatric domains and survival in older adults with chronic lymphocytic leukemia (CLL).
Authors: Rice Julia , Nipp Ryan David , Lage Daniel E , Nelson Ashley M. , Newcomb Richard , Lavoie Mitchell W. , Topping Carlisle E. W. , Ritchie Christine , El-Jawahri Areej , Johnson Patrick Connor 
Published: June 2021

12041 Background: CLL is a disease that commonly affects older adults. Although the value of geriatric assessment is increasingly being recognized in older adults with cancer, few studies have examined the relationship between baseline geriatric domains and clinical outcomes in older adults with CLL. Methods: We conducted a secondary data analysis of 369 adults diagnosed with CLL and treated in a phase 3 randomized trial of patients age ≥65 with bendamustine plus rituximab versus ibrutinib plus rituximab versus ibrutinib alone. We evaluated geriatric domains of functional status (activities of daily living [ADL], instrumental activities of daily living [IADL], Timed “Up and Go,” and number of falls in last 6 months), psychological status (Mental Health Inventory), social activity (Medical Outcomes Study [MOS] Social Activity Survey), cognition (Blessed Orientation Memory Concentration Test), social support (MOS Social Support Tangible and Emotional/Informational subscales), and nutritional status ( > 5% weight loss in the preceding 6 months). We examined associations among baseline geriatric domains with overall survival (OS) and progression-free survival (PFS) using multivariable Cox regression models. Results: The median age of patients was 71 years (range: 65-89). Most were male (67.1%) and had an ECOG performance status of 0 or 1 (96.9%). In multivariable models, the following geriatric domains were significantly associated with OS: better functional status (ADL score: HR 0.67, p = 0.012; IADL score: HR 0.98, p = 0.007); social activity score (HR 0.97, p = 0.004); and nutritional status (HR 2.58, p = 0.008). Similarly, functional status (ADL score: HR 0.77, p = 0.028; IADL score: HR 0.99, p = 0.007); social activity score (HR 0.97, p < 0.001); and nutritional status (HR 2.87, p < 0.001) were all associated with PFS. Additionally, the number of impaired geriatric domains was also associated with OS (HR 1.50, p = 0.004) and PFS (HR 1.45, p < 0.001). Timed “Up and Go”, number of falls in last 6 months, psychological status, cognition, and social support were not significantly associated with clinical outcomes. Conclusions: Geriatric domains of functional status, social activity, and nutritional status were associated with OS and PFS in this cohort of older adults with CLL. These findings highlight the importance of assessing geriatric domains to identify high-risk patients with CLL who may benefit from additional support during their treatment.
Cannabidiol (CBD) use among cancer survivors.
Authors: Bailey-Dorton Chasse Margot , Gentile Danielle , Boselli Danielle , Yaguda Susan , Greiner Rebecca 
Published: June 2021

12096 Background: Cannabidiol (CBD) is a non-psychoactive component of cannabis touted for various therapeutic effects. The Federal Drug Agency has only approved one prescription CBD product for treatment of severe epilepsy. On December 17, 2020 the Federal Trade Commission announced legal consequences for deceptively marketed CBD products in the rapidly expanding market of various CBD products; the products’ unsupported claims included CBD as a cancer treatment. Little is known about survivors use of CBD. This study explores the prevalence and nature of CBD use by cancer survivors. Methods: A link to an anonymous, electronic survey was posted on the Levine Cancer Institute and SherryStrong (Martin Truex Jr. Foundation: philanthropy for ovarian cancer) Twitter and Facebook social media platforms. Data were managed in REDCap, a secure, web-based, electronic data capture tool. Survey responses were summarized and described with frequencies and compared using Fisher’s Exact tests; p < 0.1 was considered statistically significant. Results: N = 295 self-selected respondents were White (95%), female (86%), middle aged (45-64 years) (58%) and in the US (95%). Ninety percent indicated current (85%) or past (15%) use of CBD product; a third of these participants (N = 102) identified as cancer survivors. Gynecologic (31%) and breast (30%) cancers were the most recorded malignancies, and 38% report active treatment. Most survivors indicated using CBD products daily (77%) for a year or less (79%) and spent @$30 a week on products (70%). Common uses for CBD were easing pain (66%), anxiety (50%), and sleep (50%)—14% reported treating or preventing cancer. 41% learned about CBD from family/friends, fewer learned from the Internet (21%) or local store (11%). Only 12% received information from a physician. Liquid drops (58%) and topicals (19%) were popular products and reported side effects were sparse—sedation and/or euphoria were indicated by 10% and 2%, respectively. Over 82% of cancer survivors indicated that CBD product helped their conditions. CBD use to ease anxiety and stress declined with age; 71% of young survivors (aged 18-44) sought anxiety relief versus 45% and 36% of middle age (aged 45-64) and seniors (aged 65+), respectively (p = 0.05), and 58% of young survivors pursued stress relief versus 39% of middle age and 21% of seniors (p = 0.08). More young (25%) and middle age (37%) survivors indicated spending over $30 on products weekly than seniors (7%) (p = 0.08). No differences were seen in CBD use between cancer survivors by gender or treatment status. Conclusions: Cancer survivors commonly use CBD, yet infrequently under the guidance of a physician. Survivors largely rely on word of mouth and internet information about CBD. Despite lack of standardization of production and labeling of CBD products, the majority of patients reported positive improvements in symptoms. Future research should explore strategies to educate cancer patients and providers in safe CBD use.
Transitioning ifosfamide based chemotherapy to the outpatient setting: A model of implementation of transitioning chemotherapy outpatient in a safety net hospital.
Authors: Banh Cindy , Arrendondo Alejandra , Notbohm Kassie , Valsvik Kendall , Ortega Alicia , Sanders Lauren , Recio Alejandro , Kraft Andrew , Babiker Hani M. , Do Brian , Persky Daniel O , Abraham Ivo , McBride Ali 
Published: June 2021

1540 Background: Ifosfamide displays clinical activity against germ cell tumors as well as soft-tissue and bone sarcomas. It is used in different oncology regimens and commonly administered inpatient due to patient monitoring and side effect management. Transitioning certain chemotherapy regimens to the outpatient setting provides a novel approach to treating patients while maximizing patient satisfaction and decreasing total patient care costs1. There is limited data and protocol development to transition ifosfamide regimens to the ambulatory setting. This study’s purpose is to characterize a pharmacy managed ambulatory oncology workflow for transitioning ifosfamide based-regimens to the outpatient setting. Methods: A retrospective cohort chart review was conducted at a single center and included patients 18 years and older receiving at least one cycle of ifosfamide therapy between September 1, 2013 and July 31, 2019. The primary outcome was to evaluate the side effect profile and cost of treatment of ifosfamide. The secondary endpoint included number of hospitalizations. The adverse event grading system was defined using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. The highest grade observed for adverse effects was documented for every cycle of each patient. The cost was evaluated by labs ordered, drug used, length of stay in the hospital for chemotherapy or adverse reactions. Results: Ifosfamide therapy of 86 patients (57 OP, 29 IP) was reviewed. The predominant OP regimens were adriamycin-ifosfamide-mesna (AIM) with 43.9% and ifosfamide-etoposide (IE) with 29.8%. Grade 4 anemia, thrombocytopenia, and neutropenia were most frequent in IP vs OP therapies (22.9% IP vs 4.3% OP, 21.6% IP vs 9.2% OP, and 22.8% IP vs 19.6% OP respectively). Neutropenic fever (NF) occurred in 20 OP patients which were predominantly treated with AIM or IE, and led to average hospital stay of 6 days. Neurotoxicity, treated with methylene blue (MB), occurred in 4 OP patients. OP therapy saved a total of 783 hospital days, leading to a cost savings of $2,103,921. Conclusions: Transitioning to outpatient therapy is feasible for academic and community infusion centers. Administration of chemotherapy in the outpatient setting has shown to be safe, well-tolerated, and associated with decreased total cost of care, thereby lowering costs under the oncology care model when compared with inpatient chemotherapy costs.
Comparison of checkpoint inhibitor treatment-related cutaneous adverse events in racial and ethnic minority and Caucasian cohorts at Memorial Sloan Kettering Cancer Center.
Authors: Geisler Amaris , Barrios Dulce M. , Phillips Gregory , Nouvini Rosa , Lacouture Mario E. , Noor Sarah 
Published: June 2021

2632 Background: Immune-related cutaneous adverse events (irCAEs) are the most common and often the first toxicity of immune checkpoint inhibitors (CPIs). In the general population, irCAEs occur on average within 3.6 weeks of treatment initiation and most commonly manifest as maculopapular rash, lichenoid rash, and pruritus. Less is known about these irCAEs in racial and ethnic minority patients. The purpose of this study is to compare the irCAEs of cohorts of Caucasian and racial and ethnic minority patients at Memorial Sloan Kettering Cancer Center. Methods: Herein, we conducted a retrospective chart review of racial and ethnic minority patients treated with CPIs between 2012-2019 at Memorial Sloan Kettering Cancer Center. irCAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. These were compared to a Caucasian cohort matched by demographics and cancer therapy regimen. Results: One hundred ten racial and ethnic minority patients presented to dermatology for irCAEs. Our population consisted of 59 (53.6%) females and 51 (46.4%) males with a mean age of 59 (range 20-85). Of the patients who were seen by dermatology, 63/110 were Asian (57.3%) followed by 34/110 African American (30.9%), and 1 Native American. Twelve patients were of Hispanic ethnicity (10.9%), which included those of both African American and Caucasian race. The 110 patients that were evaluated by dermatology had 221 cutaneous adverse events. Rash (96, 43.4%), pruritus (40, 18.1%), and xerosis (23, 10.4%) were most frequently diagnosed (average time from treatment start to presentation was 125 days). Dermatology identified 87 (39.3%) grade 1, 103 (46.6%) grade 2, 30 (13.5%) grade 3, and 1 (0.4%) grade 4 events. There were 17 (15.5%) treatment interruptions, including 7 patients who required permanent discontinuation. In the Caucasian cohort, mean time to onset was 228 days (range 1-1500). Dermatology identified 48 (43.6%) grade 1, 44 (40.0%) grade 2, 18 (16.4%) grade 3, and 0 (0.0%) grade 4 events, with maculopapular rash (55, 50.0%) and pruritus (25, 22.7%) most frequently diagnosed. Conclusions: Our findings suggest that irCAEs occur frequently in cancer patients from racial and ethnic minority groups, with similar grade and morphology as Caucasian patients. When irCAEs develop in this population, the diagnosis occurred later than what has previously been reported, possibly due to these patients seeing MSK oncologists with an established dermatology consultation system and insight into how to manage these patients on their own. Prospective evaluation of underrepresented minorities receiving CPI therapy is warranted in order to identify risk factors and therapeutic strategies for these untoward events, so that optimal cancer care may be delivered.
Prognostic value of plasma hPG80 (circulating progastrin), alone or in combination with Alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma.
Authors: Prieur Alexandre , Assenat Eric , Dupuy Marie , Iltache Sarah , Vire Berengere , Soulé Julien , Liaud Pierre , Cousin Thierry , Mahi Younes , Joubert Dominique 
Published: June 2021

3033 Background: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis since it is expressed in the advanced stages of the disease. Consequently, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages of the disease. hPG80 (circulating progastrin), a new drug target for cancer treatment which plays a pivotal role in tumorigenesis, is present in the blood of multiple types of cancers at early stages including HCC. The purpose of this study was to evaluate the prognostic value of plasma hPG80 in patients with HCC, in combination or not with AFP. Methods: A total of 168 HCC patients (BCLC from 0 to D) managed with local or systemic treatments, (“Liverpool” biobank) were enrolled prospectively and analyzed retrospectively. hPG80 was quantified using DxPG80 Lab kit (ECS-Progastrin) and AFP was quantified using Cobas E411 in the blood of HCC patients. An optimal cutoff value of hPG80 was identified at 4.5 pM by calculating the minimal p-value based on the log-rank method. For AFP, a cutoff of 100 ng/mL was used as for liver transplantation (Notarpaolo, 2016). The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. Results: The median overall survival (OS) of the full cohort is 20.9 months. HCC patients with high hPG80 levels (hPG80+: >4.5 pM, 105/168) had significantly lower median OS compared to patients with low hPG80 levels (hPG80-: <4.5 pM, 63/168) (12.4 months versus undefined respectively, p < 0.0001). Patients with high AFP (AFP+: >100 ng/mL, 69/165) had significantly lower median OS compared to patients with low AFP (AFP: <100 ng/mL 96/165) (7.2 months versus undefined, p < 0.0001). To improve the stratification, the patients were further categorized into four groups: hPG80-/AFP- (n = 42), hPG80+/AFP- (n = 54), hPG80-/AFP+ (n = 21) and hPG80+/AFP+ (n = 48). In the AFP- group, hPG80+ patients exhibited a significantly worse prognosis than those with hPG80- (26.3 months versus undefined, p=0.0087). Similarly, in the AFP+ group, patients with hPG80+ had a significantly worse survival compared to hPG80- patients (5.7 months versus 13.4 months, p = 0.0391). Finally, we evaluated the median OS of AFP+ patients according to BCLC staging. Interestingly, in the group BCLC 0 to B, hPG80+ had a significantly worse prognosis than those with hPG80- (15.8 months versus 40.25 months, p=0.0317). Conclusions: Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and worst prognosis, especially for those patients with negative AFP and early-stage HCC.
Phase Ia study of CBP-1008, a bi-specific ligand drug conjugate targeting FRα and TRPV6, in patients with advanced solid tumors.
Authors: Gong Jifang , Hu Xichun , Zhang Jian , Du Yiqun , Huang Robert , Teng Yan , Tan Wei , Shen Lin 
Published: June 2021

3077 Background: CBP-1008 is a first-in-class bi-specific ligand drug conjugate targeting folate receptor α (FRα) and vanilloid subfamily member 6 of transient receptor potential channels (TRPV6) with a high potency tublin inhibitor payload, monomethyl auristatin E (MMAE). A first-in-human, multicenter, phase I study of CBP-1008 (NCT 04740398) is ongoing, and we herein report the preliminary result of part A which is to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of CBP-1008 in solid tumors. Methods: Dose escalation commenced in single-patient cohorts for the first 2 planned dose levels and then followed by a standard 3 + 3 scheme. CBP-1008 was administered as intravenous infusion at escalating doses (0.015, 0.03, 0.12, 0.15, and 0.18 mg/kg). The primary endpoints were to determine the safety and maximum tolerated dose (MTD). Adverse events (AEs) and dose-limiting toxicities (DLTs) were evaluated. Results: Eighteen patients with advanced solid tumors who had failed multiple systemic treatment regimens were enrolled. The diseases include colorectal cancer (n = 7), breast cancer (n = 5), non-small cell lung cancer (n = 2), ovarian cancer (n = 2), adrenocortical carcinoma (n = 1), and follicular dendritic cell sarcoma (n = 1). The DLTs observed included grade 4 hypophosphatemia (0.15 mg/kg), grade 4 neutropenia (0.12, 0.15, and 0.18 mg/kg), grade 4 febrile neutropenia (FN) (0.18 mg/kg), grade 3 hyperglycemia (0.15 mg/kg), and grade 3 alanine aminotransferase (ALT) elevation (0.18 mg/kg). The most common all grade AEs suspected to be drug-related were fever (83.3%, totally limited to grade 1-2), aspartate aminotransferase (AST) elevation (72.2%, 5.6% evaluated as grade 3-4), leukopenia (66.7%, 27.8% as grade 3-4), neutropenia (66.7%, 38.9% as grade 3-4) and hypohemoglobinemia (55.6%, 5.6% as grade 3-4), with no drug-related deaths. MTD is estimated between 0.15 mg/kg and 0.18 mg/kg Q2W. Best overall response was partial response (PR) in 1 patient at 0.18 mg/kg and 4 patients (22.2%) achieved stable disease (SD). Responses occurred in patients with FRα and/or TRPV6 -positive expression advanced solid tumors. Conclusions: CBP-1008 has demonstrated acceptable safety profile. Tumor response correlating with dosing and FRα/TRPV6 receptor expression levels has been well observed. Clinical trial information: 04740398.