bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single center experience with alpelisib-fulvestrant in heavily pretreated women with HR(+), HER-2 (−) metastatic breast cancer.
Authors: Tryfonopoulos Dimitrios , Tzouda Vasiliki , Zouki Dionysia , Kyriakidou Athina , Sarris Evangelos , Grivas Anastasios , Gouveris Panagiotis , Papaxoinis George , Demiri Stamatina G 
Published: June 2022

e13034 Background: HR-positive, Her2-negative metastatic breast cancer patients harboring PIK3CA mutations are associated with resistance to endocrine therapy and worse prognosis. Results from the phase III SOLAR-1 trial demonstrate improved PFS for patients treated with Alpelisib-Fulvestrant after failure on first or second line treatment with aromatase inhibitor. Methods: Within an early access program for Alpelisib in a single oncology center, patients diagnosed with metastatic HR-positive, Her2 -negative breast cancer were screened for PIK3CA mutations. New generation sequencing (NGS) was the preferred technique to identify carriers with PIK3CA mutations on soft tissue or liquid biopsy. Patients who progressed and carried PIK3CA mutations received Alpelisib and fulvestrant as subsequent line of therapy. Results: Among 32 patients (pts) screened, 13 (40,6%) had a PIK3CA mutation. In total, 11 pts received alpelisib. Median age at diagnosis was 57.5 years (range, 39-69). Eight pts (72.7%) had been operated for early-stage breast cancer, 6 (54.5%) had received adjuvant chemotherapy and 5 (45.5%) had received adjuvant radiotherapy. Of 11 pts with evaluable histology, 3 pts (27.3%) had high grade tumors at diagnosis. Ten pts (90.9%) had PR positive tumors. Median Ki67 was 20% (range, 2-80). Eight pts (72.7%) had PIK3CA exon 20 and 3 (27.3%) had exon 9 mutations. Six pts (54.5%) had received prior chemotherapy in the metastatic setting and 10 (90.9%) prior CDK4/6 inhibitor. Three pts (27.3%) received Alpelisib as 2nd line and all remaining patients received alpelisib beyond 3rd line treatment. All pts (100%) had metastasis to the bones, 8 pts (72.7%) to the liver, 6 pts (54.5%) to the lungs and 2 pts (18.2%) to the brain. Until the date of last assessment, Alpelisib was administered for a median of 5.1 months (range, 0.4-21.3). Ten pts were evaluable for response to treatment with Alpelisib. One (10%) had CR, 5 (50%) SD and 4 (40%) PD as best response. Median duration of disease control was not reached. Baseline characteristics were not associated with disease control. Adverse events noticed were thrombocytopenia grade II (1/11), diarrhea grade II (2/11), skin rash grade I &II (4/11), weakness grade III (1/11) and hyperglycemia (3/11). Conclusions: Prevalence of PIK3CA mutations is consistent with published data. Furthermore, combination of Alpelisib-Fulvestrant is a highly active line of therapy even in heavily pretreated patients.
Incidence and severity of neutropenia in patients treated with cyclin-dependent kinase 4/6 inhibitors (CDKi) for metastatic breast cancer.
Authors: Singh Anmol , Giordano Sharon H. , Zhang Ning , Chavez Mac Gregor Mariana , Zhao Hui 
Published: June 2022

e13036 Background: Palbociclib (P), ribociclib (R), and abemaciclib (A) are FDA approved CDKi used in combination with endocrine therapy for first- and second-line treatment of metastatic breast cancer. Neutropenia is a commonly encountered adverse effect with these agents. This analysis aimed to identify the incidence and severity of neutropenia in patients receiving CDKis. Methods: This retrospective, observational study used administrative data from the Optum’s de-identified Clinformatics® Data Mart Database (January 2016-June 2020) to identify patients treated with P, R, or A and who had at least two ICD-9 or ICD-10 diagnosis codes for breast cancer separated by >30 days. Using claims, neutropenia was defined as either one inpatient diagnosis code or 2 outpatient diagnosis codes from the time of the patient’s first CDKi prescription claim to the time of the last claim plus 42 days. For the subset of patients who had laboratory results during their period of treatment with CDKi, neutropenia was defined as an absolute neutrophil count (ANC) <1500 and severe neutropenia as ANC <500. Descriptive statistics and logistic regression models were used to characterize the population and to identify risk factors for development of neutropenia. Results: Of the total of 8,158 included patients, 82% were treated with P, 4.1% with R, 7.5% with A, and 6.4% with more than one CDKi. Patient age ranged from 28 to 91 years (median= 68 years). Median follow up from initiation of CDKi until the end was 194 days. 17.5% patients had ICD claims indicating neutropenia but only 1.6% were hospitalized with a diagnosis of neutropenia. Neutropenia codes were observed in 31.6% patients treated with P, 24.6% patients treated with R, and 15.6% patients treated with A. Among the 4766 patients who had laboratory results, 81% were treated with P, 4% with R, 7% with A, and 8% with more than one CDKi. 31.6% of patients had neutropenia defined by ANC < 1500. Severe neutropenia was seen in 10.8% of patients treated with P, 5.7% of those treated with R, and 5% of those treated with A. In a logistic regression model among the patients with lab results, patients treated with P had increased odds of neutropenia compared to those treated with A (OR 1.84, 95% CI 1.40-2.43) but patients treated with R vs A did not (OR 1.46, 95% CI 0.95-2.25). Asian and Hispanic patients had higher odds of neutropenia (OR 1.7, 95% CI 1.2-2.4, OR 2.1, 95% CI 1.8-2.6, respectively) compared to Whites, but Black patients had lower risk than White patients (OR 0.8, 95% CI 0.6-0.9). Conclusions: Neutropenia remains a common side effect of CDKis, although the frequency of severe neutropenia is low. Of the three CDKis, P was associated with the highest rate of neutropenia.
Treatment of alpelisib induced hyperglycemia with sodium-glucose cotransporter-2 inhibitors: A single institution experience.
Authors: Brugioni Emily , Pluard Timothy J. , Cathcart-Rake Elizabeth Jane , Gosch Kensey 
Published: June 2022

e13041 Background: PIK3CA mutations occur in about 40% of patients with HR+/HER2- breast cancer. The phase III SOLAR-1 trial demonstrated prolonged progression-free survival with alpelisib and fulvestrant compared to fulvestrant alone among patients with HR+/HER2-/ PIK3CA mutant advanced breast cancer previously treated with endocrine therapy. Hyperglycemia was seen in 64% of patients treated with alpelisib and fulvestrant and was treated with metformin. Inhibition of PI3Kα leads to an on-target effect of hyperglycemia and a secondary hyperinsulinemia. This rebound hyperinsulinemia may lead to escape PI3K pathway activation in breast cancer progression via the insulin and IGF1pathways. Concurrent administration of SGLT2 inhibitors may abrogate the PI3K pathway activation effect and delay disease progression. This study reports time on treatment with alpelisib and PFS among patients who received an SGLT2 inhibitor with alpelisib. Methods: A retrospective review of all metastatic breast cancer patients treated with alpelisib was completed from 8/2019 to 5/2021 at the Saint Luke’s Koontz Center for Advanced Breast Cancer. Results: This review included 22 female patients, 11 received an SGLT2 inhibitor for treatment related hyperglycemia (A+SGLT group) and 11 who received metformin/other diabetic agents (A group). Baseline characteristics were not significantly different between the two groups: median age 63, BMI of 29.1, hemoglobin A1C of 6.3 and fasting blood glucose of 119.1mg/dl. PIK3CA mutations included H1047X (40.9%), E545X (31.8%), E542K (13.6%), other (13.6%). The median number of prior treatments for MBC was 3 (range 1-5). Prior treatments included aromatase inhibitors: 100%, fulvestrant: 77%, CDK 4/6 inhibitors: 82%, everolimus: 32% and chemotherapy: 68%. Hyperglycemia grade 2+ was seen in 72.7% of patients. There were no significant differences between the two groups for emergency room visits, hospitalizations, or endocrinology referrals related to hyperglycemia. Median time to initiation of an SGLT2 inhibitor was 13 days following the first dose of alpelisib. PFS was longer in the A+SGLT compared with the A group with a median time to progression of 6.1 months and 3.9 months respectively (HR 0.51; 95% CI 0.16 to 1.63; p = 0.39). Time on treatment was significantly longer for A+SGLT group compared with the A group, with a median time on treatment of 5.8 months, compared with 3.0 months (HR 0.32; 95% CI 0.11 to 0.92; p = 0.03). The primary reason for discontinuation of alpelisb was disease progression in 73%, with no statistically significant difference in the reason for discontinuation between the groups. Conclusions: This study supports a potential clinical benefit of an SGLT inhibitor along with alpelisib in allowing for a longer time on treatment, without significant adverse events. It also suggests a possible favorable impact on PFS for the combination.
Atrial fibrillation is associated with worse outcomes in patients with breast cancer.
Authors: Gad Mohamed M. , Saad Anas M. 
Published: June 2022

e13043 Background: The incidence of atrial fibrillation (AF) is higher in women with breast cancer (BC) compared to aged-matched controls. A better understanding of the clinical outcomes in women with BC and AF can help stratify patients’ risk and inform clinical decision making. Methods: Females with active BC diagnosis hospitalized from January 2010 to December 2018 for any cause were identified in the Nationwide Readmissions Database (NRD). Hospitalizations were divided to females with AF and those without a known diagnosis of AF. The primary outcome was in-hospital mortality. Multivariate logistic regression analysis was performed to adjust for differences in baseline characteristics. All statistical analyses were conducted using the weighted values of observations as provided by the NRD to measure national estimates. Results: A total of 1,596,853 hospitalizations of BC were identified. Out of those, 119,307 (7.5%) had AF. Females with AF were older, median age 77 [IQR 69-84] versus 61 [51-71]. AF patients had higher rates of chronic pulmonary disease, 23.0% versus 14.3%, p < 0.001; hypothyroidism, 20.9% versus 13.1%, p < 0.001; peripheral vascular disease, 6.8% versus 2.5%, p < 0.001; pulmonary hypertension, 4.8% versus 1.6%, p < 0.001; cardiac valvular disease, 9.5% versus 2.3%, p < 0.001; hyperlipidemia, 39.9% versus 24.0%, p < 0.001; diabetes mellitus, 28.9% versus 19.8%, p < 0.001; heart failure, 37.0% versus 7.5%, p < 0.001; prior bypass surgery, 4.1% versus 1.2%, p < 0.001; prior stroke, 7.8% versus 2.5%, p < 0.001; and prior myocardial infarction, 6.0% versus 2.2%, p < 0.001. In-hospital mortality was significantly higher in patients with AF, 7.1% versus 4.1%, p < 0.001. Adjusted Odds Ratio (aOR) for in-hospital mortality was higher in AF, aOR 1.42, 95% CI (1.38-1.46), p < 0.001. Conclusions: Atrial fibrillation is associated with a higher risk of in-hospital mortality in patients with breast cancer regardless of the reason of hospitalization. Stratifying patients based on AF presence can help inform clinicians and patients of the patients’ risk of mortality during hospitalization.
PD-L1 immune cell expression levels and clinical outcomes in advanced triple-negative breast cancer treated with atezolizumab.
Authors: Ovcaricek Tanja , Dobovisek Luka , Gasljevic Gorana , Stefanovski Dimitar , Borstnar Simona 
Published: June 2022

e13066 Background: Treatment with immune checkpoint inhibitors (ICI) has become a standard of care for metastatic PD-L1 positive TNBC patients and PD-L1 has emerged as an important predictive biomarker. Predictive differences of PD-L1 were found in response to immunotherapy in different studies. Alterations in DNA repair pathways (aDDR) have also been investigated as a predictive biomarker for ICI due to the increased mutations and neoantigen production. Real-world data regarding outcomes of treatment of metastatic (m)TNBC patients (pts) with ICI and predictive value of PD-L1 and aDDR is lacking. In this study PD-L1 and aDDR were evaluated for association with clinical benefit of treatment with atezolizumab and nab-paclitaxel (A+nP) in PD-L1 positive mTNBC patients treated in routine clinical practice. Methods: Medical records from 41 PD-L1 positive mTNBC patients consecutively treated with A+nP at Oncology Institute Ljubljana between April 2019 and October 2021 were collected for the present study. PD-L1 expression was assessed on immune cells (IC) as percentage of tumor area using VENTANA SP142 PD-L1 IHC assay (<1% [PD-L1 negative] vs. ≥1% [PD-L1 positive). Patients were divided into 2 subgroups based on PD-L1 status, high (PD-L1≥ 5%) and low (PD-L1 ≥1% and <5%). Germline alteration status in DDR genes was determined on blood samples. We used Kaplan-Meier survival curves to calculate median (m) PFS and OS . The prognostic impact of PD-L1exspresion levels and aDDR was calculated using Cox model. Results: Median follow up of the study was 22 months. Majority of patients had low PD-L1 status (25/41, 61%) and 54% of evaluable patients (15/28) were found to harbor deleterious alterations in DDR genes, of them BRCA1 in 9 pts, BRCA2 in 2 pts, and PALB2, CHEK2, CHD1, RAD51D in 1 pts. Median PFS in the entire cohort was 8.26 months; 95% CI (3.54-12.98) and mOS 20.49 months; 95% CI (11.3-29.7). Significant survival benefit was observed among patients with high PD-L1 status treated with A+nP. No difference in survival was found in patients harbouring germline mutations (aDDR positive) versus without mutations (Table). Conclusions: PD-L1 positive mTNBC patients with high PD-L1 status (≥5%) had almost three times less risk of progression and death compared to low PD-L1 status (≥1% and <5%). Presence of aDDR showed no effect on disease outcome. [Table: see text]
Preanalytical protocols for improving access to live tissue diagnostics in remote and low resource settings.
Authors: Charania Areesha A. , Patel Heli K. , Punjani Zeenia , Patel Zeelu H. , Papachristou Georgios , Contreras Carlo M. , Tsung Allan , Budhwani Karim I. 
Published: June 2022

e13501 Background: Nearly 70% of diagnostics lab test errors occur due to variability in preanalytical factors. Preanalytical factors comprise parameters from the time tissue is extracted from the patient to the time it is tested in the lab. For lack of standardized preanalytical protocols, integrity of collected specimens is often compromised. This is particularly pronounced when specimens are collected in remote or low resource settings and shipped to testing facilities. Establishing preanalytical protocols could serve as an important resource for remote collection sites and substantially reduce variability in the integrity of specimens thereby improving lab test rigor and reproducibility and promote innovation in live tissue diagnostic tests for personalized medicine. Objective: The aim of this study is to analyze impact of cold chain logistics on integrity of collected solid tumor tissue specimens. Specifically, duration in transit, container and wet ice packing, and composition of transport media were assessed. Methods: Baseline protocols for biospecimen preanalytical parameters were established from literature review. Standard aseptic lab protocols were implemented for all experiments including preparation of transport media, tissue transport kits, transport kit packaging, tumor tissue transfer in tissue transport kits, tissue receiving, and tissue integrity assessment. Transport was simulated for human and murine pancreatic ductal adenocarcinoma (PDAC) tissue by holding packaged tumor tissue containers in storage for the duration of transport. Saline solution, basal media, and complete media were evaluated as transport media. Specimen integrity was evaluated using live/dead assays in high-content imaging systems at 24- and 48-hour intervals. Results: For human and murine tumor tissue, viability was optimal when tissue was transported in Nalgene jars containing complete media packaged in ¼” thick wall Styrofoam containers tightly packed in wet ice for transport. While specimens fared well over both 24- and 48- hour simulated shipping durations, temperature and humidity logs from sensors embedded in the packages showed sharp degradation in packaging environment with longer durations of time. Conclusions: Establishing preanalytical protocols would improve rigor and reproducibility in diagnostic lab tests by improving tissue viability and integrity. Such protocols would also enable next generation cancer models to further enhance predictive capacity in translational research and subsequently in personalized medicine applications at the bedside.
Availability of child care resources for patients undergoing cancer treatment at NCI-designated cancer centers.
Authors: Levine Monica , Brown Melissa , Nagel Christa , Vargas Roberto , Chambers Laura 
Published: June 2022

e13508 Background: The National Cancer Institute (NCI) estimates that approximately one-quarter of adults with cancer are parents to children less than 18 years. Further, it is estimated that 2.85 million minor children in the United States have a parent undergoing cancer treatment. Previous studies have demonstrated that parents with cancer experience significant stress and disruptions to familial life following a cancer diagnosis. In a study of women with breast, gynecologic cancer and other cancers undergoing cancer therapy, 48.7% of women endorsed needing help with childcare and 64.1% needing help with household management. Despite this evidence supporting both a need for childcare among patients with cancer, data regarding the availability of on-site childcare programs and resources at NCI-designated cancer centers is limited. The objective of this cross-sectional study was to assess the availability of childcare resources for parents who are undergoing cancer treatment at NCI-Designated Cancer Centers. Methods: The availability of childcare resources for parents undergoing cancer treatment at all 51 NCI-designated comprehensive cancer centers and 13 NCI-designated cancer was assessed in January 2021 and February 2021. Childcare resources were assessed via online search and telephone calls. Specifically, centers were queried regarding availability of daycare programs for children of patients undergoing treatment and whether resources were available to assist patients in need of childcare. Descriptive statistics were performed. Results: In total, only 1/64 (1.6%) of NCI-designated cancer centers currently offer childcare resources for patients undergoing cancer treatment. This center offers childcare for children ages 2–8, free of charge with multiple outpatient locations. One additional institution previously provided patients with access to daycare, but has closed due to the COVID-19 pandemic. Further, only 1/64 (1.6%) NCI-designated cancer center offers financial assistance grants to aid patients to subsidizing childcare costs during cancer treatment. Conclusions: Institution sponsored options for childcare for patients undergoing cancer treatments are highly limited, even in the best resourced cancer care settings. The COVID-19 pandemic has limited options further, and many hospitals now restrict visitors under the age of 18. Patient grants or institutionally sponsored childcare provider networks may represent an avenue for supporting parents who are facing a cancer diagnosis. Supporting families of patients with cancer has great potential to impact quality of life, economic and psychological stress.
Impact of turnaround time (TAT) of molecular testing on initial treatment (Tx) in newly diagnosed stage 4 non-small cell lung cancer (NSCLC 4): An Integra Connect (IC) retrospective observational study.
Authors: Gart Mike , Gordan Lucio N. , Choksi Rushir J. , Petro Daniel P. , Scott Jeffrey A. , Varughese Prateesh , Alwon Erin , Smith Robert E. 
Published: June 2022

e13510 Background: Broad molecular profile-based initiation of Tx in newly diagnosed NSCLC 4 (KF Mileham, Cancer Med, 2022) is advocated by NCCN guidelines. Despite this, Tx is often started prior to, and without knowledge of, an actionable oncogenic driver (AOD), and often without subsequent switch to appropriate tyrosine kinase inhibitor (TKI). In this study we sought to assess the impact of TAT of genomic testing on Tx in patients harboring a potentially actionable EGFR mutation. Methods: By interrogating the IC curated database, we identified 2,357 newly diagnosed NSCLC 4 patients (pts) who started an initial line of therapy (LOT 1) between 1/1/2019 and 12/31/2021. Squamous carcinoma pts were excluded unless documented to be never smokers or <age 40. We assessed testing across all sample types and performed the analysis on solid tumor tissue next-generation sequence (NGS) tested patients. We used an order for EGFR as a surrogate for AOD evaluation and collected date of order and reporting of EGFR test results, and date of 1st Tx start. From this, we calculated TAT and whether Tx was initiated after genomic results. In addition, we captured whether testing was in-house or by reference lab (RL). We looked at the RLs that comprise of the top 85% of NGS test sources, where the testing source was known. We removed records where test order dates and results dates were the same date, where test order dates or results dates were unknown, and where TAT > 90 days. EGFR Effective Testing Rate (EETR) is defined as EGFR result prior to line 1 Tx start. Results: Median age was 70 (range 40 - 89) and 50% male. Pts with TAT of ≤7 days had an 82% EETR vs. Pts with TAT of >29 days had a 61% EETR. Overall, RLs had a median TAT of 19 days with a 72% EETR, whereas in-house labs had a median TAT of 15 days with a EETR of 80%. Conclusions: When providers and patients can obtain test results within 21 days of test order there is a higher likelihood of waiting for the test result to start Tx. Many community oncology practices are contemplating implementing in-house testing solutions to improve rates of testing and turnaround time of testing. This may prove to be an effective strategy given the better TAT for in-house testing. When there is faster TAT, patients and providers wait to start initial Tx. Getting patients on appropriate therapy based on their biomarker status can improve overall survival.[Table: see text]