bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-year disease-free survival in randomized trials of chemotherapy and HER2-targeted therapy: A meta-analysis.
Authors: Mittal Abhenil , Tamimi Faris , Molto Consolacion , Meti Nicholas , Al-Showbaki Laith , Wilson Brooke , Amir Eitan 
Published: June 2022

579 Background: The Katherine trial reported a 3-year invasive disease-free survival (DFS) of 77% in patients not achieving pathological complete response (pCR) and continuing on adjuvant trastuzumab. Case series suggest better outcomes and data support that some patients with residual disease have similar outcomes to those with pCR (Steenbruggen et al). The absolute benefit of adjuvant trastuzumab emtansine (T-DM1) would be smaller in patients with favourable outcomes despite residual disease. As such, a more precise estimate of 3-year DFS is needed for treatment planning. Methods: We reviewed reports of randomized trials of neoadjuvant chemotherapy and HER2-directed therapy and extracted the 3-year DFS, a validated surrogate endpoint in HER2-positive early-stage breast cancer. Data were extracted for patients with residual disease and with pCR. The mean 3-year DFS weighted by study sample size was calculated. Meta-regression comprising linear regression weighted by sample size (mixed effects) was performed to explore associations between 3-year DFS and trial-level patient, disease and treatment factors and changes in 3-year DFS over time. Quantitative significance was explored using methods described by Burnand et al. Results: Eleven studies comprising 3908 patients were included in the analysis. The mean 3-year DFS for patients with pCR and for residual disease was 90.1% and 80.0%, respectively. DFS improved over time. For trials whose final year of accrual was after 2010, mean 3-year DFS for residual disease was 84.7% compared to 78.0% for trials completing accrual before that time (p<0.001). In a subgroup analysis of patients with residual disease, those receiving dual HER2-targeted therapy in the neoadjuvant setting had a 3-year DFS of 85.3% compared to 73.3% for those receiving only trastuzumab (p<0.001). Meta-regression results for residual disease are shown in the Table. Positive quantitative significance was observed for final year of accrual, ER-expression, dual anti-HER2 therapy and concurrent vs sequential anti-HER2 therapy. Negative quantitative significance was observed for larger clinical tumor size and nodal involvement. Conclusions: 3-year DFS for patients with residual disease and HER2-targeted therapy is better than reported in the Katherine trial and has improved over time, possibly due to increased use of dual HER2-targeted therapy in the neoadjuvant setting. In this context, the absolute benefit of adjuvant T-DM1 may be smaller than anticipated. [Table: see text]
Dapagliflozin associated to sacubitril/valsartan and relationship with cardioprotection in human cardiac cells exposed to doxorubicin and HER2-blocking agents through MyD88, NLRP3 mediated pathways.
Authors: Maurea Nicola , Quagliariello Vincenzo , Iovine Martina , Buccolo Simona , Paccone Andrea , Bisceglia Irma , De Laurentiis Michelino 
Published: June 2022

587 Background: The cumulative incidence of cardiac events in breast cancer patients treated with anthracycline and trastuzumab at 1 year after the diagnosis of cancer was 16.4%, at 2 years 23.8 %, and at 3 years 28.2%. Sodium glucose co-transporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality. LCZ696 (neprilysin inhibitor + valsartan) as able to lower the risk of cardiovascular events in chronic heart failure. We hypothesize that dapagliflozin associated to LCZ696 could exerts cardioprotective effects in cellular models of doxorubicin and trastuzumab-induced cardiotoxicity. Methods: Human cardiomyocytes (HL-1 cells) were exposed to subclinical concentration of doxorubicin and trastuzumab (100 nM) alone or in combination with dapagliflozin (50 nM) or LCZ696 (at 100 mM) or both in combination for 48h. Cell viability, apoptosis and necrosis were performed. Quantification of malondialdehyde, 4-hydroxynonenal and intracellular Ca2+ were performed through spectrophotometric methods. Anti-inflammatory studies were also performed (expression of NLRP3 inflammasome, TLR4/MyD88 pathways, nuclear expression of NF-kB). Intracellular concentration of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF were also performed. Results: Dapagliflozin and LCZ696 increased synergistically the cell viability during exposure to doxorubicin and trastuzumab. Combination of dapagliflozin and LCZ696 reduces intracellular Ca2+ overload (-68,4% vs cells treated only to anticancer drugs; p<0,001), lipid peroxidation (mean reduction of 57-63,4 % compared to cells exposed only to anticancer drugs; p<0,05). The expression of MyD88, NLRP3 and NF-kB were strongly reduced after treatment with dapagliflozin and LCZ-696 (-52,5, -43,7 and -57,3 % vs cells exposed only to anticancer drugs, respectively; p<0.05). Notably, combination of dapagliflozin and LCZ-696 enhanced the expression Of IL-10; contrary, pro-inflammatory cytokines were reduced, such as IL-1α, IL-1β, IL-6, IL-8, IL17-α and IL-18 (p<0.05). Conclusions: During exposure to doxorubicin and trastuzumab, dapagliflozin associated to LCZ-696 exerts additive cardioprotective and anti-inflammatory effects compared to each drug alone. Their properties are mediated by the reduction of iCa2+ content that consequently reduces peroxidation and NLRP3- MyD88 expression. These results indicating the potential use of SGLT-2 inhibitors associated to LCZ696 in preclinical models of cardiotoxicity.
Prediction of response to neoadjuvant therapy (NAT) in early breast cancer (EBC) at community hospitals: SimBioSys TumorScope Validation Study.
Authors: Pfeiffer John R. , Zwicky Karen , Pandey Tushar , Antony Anu K. , Team The SimBioSys , Cole John A. , Wolf Clifford 
Published: June 2022

598 Background: While most cancer patients are treated at community hospitals, specialized equipment, diagnostic tests, and therapeutic regimens are generally validated at academic settings. Here we present a novel approach to precision medicine to improve outcomes in breast cancer care in the community setting. TumorScope (TS) is a biophysical modelling platform that uses only pretreatment standard of care (SoC) diagnostic data (demographics, drug regimen, imaging (DCE MRI) & pathology) to construct a 3D model of the tumor. TS integrates models for tumor morphology, metabolism, vascularity, and drug behavior and simulates predicted tumor response longitudinally to NAT. With this information TS predicts the reduction in tumor volume and the pathological complete response (pCR), a surrogate marker of long-term outcome, to anticipated NAT in EBC. Methods: We performed a single center validation study to show the clinical applicability of TS. Patients at Northwest Community Healthcare that received NAT with corresponding pretreatment MRI were identified in a chart review. A validation set, independent from the training set, was generated from this list and data processed through TS (n=50). Pretreatment patient SoC diagnostic data was loaded into TS. TS predicted the weekly volumetric response throughout the treatment, and it simulated residual volume to predict pCR. The validation was performed using ground truth from post treatment assessment of pCR, radiographic volumes extracted from MRIs. Results: TS predicted pCR, prospectively defined as a simulated residual tumor volume <0.01 cm3 or a 99.9% or greater reduction in tumor volume. Performance metrics of TS were calculated. TS tumor volume prediction accuracy had an area under the curve (AUC)=0.947 with sensitivity and specificity of 93.3% and 94.3% respectively. Performance was robust across all subtypes (See Table 1). TS predicted the reduction in tumor volume with a median absolute volumetric error of 3.4% as compared to radiographic volume from pre-surgery MRIs (n=50). Conclusions: In summary, TS accurately predicts patient-specific tumor volume reduction and pCR prior to NAT in EBC using only SoC pretreatment data, which could lead to a more personalized cancer care for the patient. Moreover, we demonstrate the feasibility of implementing TS at community hospitals. [Table: see text]
Deep learning algorithm to predict pathologic complete response to neoadjuvant chemotherapy for breast cancer prior to treatment.
Authors: Choi Rachel , Joel Marina , Hui Miles , Aneja Sanjay 
Published: June 2022

600 Background: Pathologic complete response (PCR) to neoadjuvant chemotherapy (NAC) is associated with improved disease-free survival and overall survival in patients with breast cancer. Predicting PCR at the patient level prior to treatment initiation would allow physicians and patients to focus on therapies with the highest likelihood of success and minimize unnecessary toxicities from chemotherapy. We hypothesize that pre-treatment prediction of PCR is possible through a deep neural network algorithm trained on breast MRI imaging obtained prior to treatment. Methods: 126 tumors from patients treated with neoadjuvant chemotherapy for T3 stage breast cancer at a single institution from 2002 to 2006 were analyzed. In total, 3780 MRI slices were included. 3 MRI contrast phases (pre, immediate post, delayed post) from each slice were used as individual inputs to create separate model predictions of PCR. The 2-D CNN was trained over 50 epochs on the training set. The model was tested on the isolated test set (30% of samples). Results: Average model prediction accuracy over the total test set using a single phase of contrast (pre-, immediate post-, or delayed post-) was 90.4%. Concordance adjustment was conducted, with exclusion of slices that had produced discordant predictions across different contrast phase inputs. This resulted in an increase of overall model accuracy to 97.6%. Model accuracy was similar across subsets of age and tumor size despite differences in PCR rates. However, model accuracy was significantly lower in the triple-negative disease group. Conclusions: We demonstrate a deep neural network that accurately predicts PCR based on breast MRI imaging taken prior to NAC initiation. Our findings represent the promise of deep learning algorithms in providing personalized prognostic data for physicians and patients. [Table: see text]
The effect of a multilevel community health worker-led intervention on health-related quality of life, patient activation, acute care use, and total costs of care: A randomized controlled trial.
Authors: Patel Manali I. , Kapphahn Kris , Salava Deb , Orchard Pat , Curry Regina , Filazzola Anne , Riley Angela , Krajcinovic Ivana 
Published: June 2022

6500 Background: Low-income and minority populations have less activation in their cancer care, lower health-related quality of life, greater acute care use and total costs of care than affluent and white populations. Community-based interventions are needed to improve patient experiences and quality of cancer care equitably among these populations. We used community-based participatory methods to refine a previously tested intervention for use in urban communities. The intervention, LEAPS, uses community health workers trained to activate patients in discussions with their cancer clinicians regarding advance care planning and symptom-burden and to connect patients with community-based resources to overcome social determinants of health. We conducted a randomized controlled trial of LEAPS in collaboration with an employer-union health plan in Atlantic City, NJ and Chicago, IL. Members of the employer-union health plan with newly diagnosed with hematologic and solid tumor cancers were randomized to the 6-month LEAPS intervention. The objective of the study was to determine whether LEAPS improved quality of life (primary). Secondarily, we evaluated the effect of LEAPS on patient activation, acute care use, and total costs of care. Methods: We used generalized linear regression models to evaluate differences in quality of life and patient activation scores between groups from baseline to 4- and 12-months post-enrollment and regression models offset for length of follow-up to compare emergency department use, hospitalizations, and total costs of care. Results: A total of 160 patients were consented and randomized into the study (80 intervention; 80 control). There were no differences in demographic or clinical factors across groups. The majority were non-White (74%), female (53%), mean age 57 years with breast (31%) or lung cancer (21%) and Stage 3 or 4 (63%) disease. At 4- and 12-months follow-up, the intervention group had greater improvements in quality of life overtime as compared to the control group (difference in difference: 11.5 p < 0.001) and greater change in patient activation overtime (difference in difference: 11.9 (p < 0.001)). At 12-months follow-up there were no differences in emergency department use (0.44 (0.71) versus 0.73 (0.22) p = 0.22) however intervention group participants had fewer hospitalizations (1.55 (0.86) vs. 2.29 (1.31), p = 0.002) and lower median total costs of care ($72,585 vs. $153,980, p = 0.04). Conclusions: Integrating community-based interventions into clinical cancer care delivery for low-income and minority populations can significantly improve patient activation, reduce hospitalizations and total costs of care. These interventions may represent a sustainable resource to facilitate equitable, value-based cancer care. Clinical trial information: NCT03699748.
Association of Medicaid expansion under the Affordable Care Act and overall survival among children with cancer.
Authors: Barnes Justin Michael , Neff Corey , Kruchko Carol , Barnholtz-Sloan Jill , Ostrom Quinn T , Johnson Kimberly J. 
Published: June 2022

6507 Background: State Medicaid expansions under the Affordable Care Act are associated with increased Medicaid coverage among children, including those with cancer. Since the expansions did not directly affect Medicaid eligibility criteria for children, these changes suggest “welcome mat” effects, where previously uninsured children become enrolled in Medicaid after their parents gain coverage. Insurance improvements from the expansions have been associated with improved cancer outcomes for non-elderly adults. However, it is unclear whether the expansions also impacted childhood cancer outcomes. Methods: Data for children ages 0-14 years diagnosed with cancer from 2011-2017 were queried from central cancer registries covering cancer diagnoses from 43 states as part of the Centers for Disease Control’s National Program of Cancer Registries. The primary outcome was 2-year overall survival. We utilized difference-in-differences analyses to compare changes in 2-year survival from 2011-2013 to 2014-2017 between children who resided in states expanding Medicaid by 2014 vs. states not expanding Medicaid within the study period. Analyses were adjusted for covariates including age, race/ethnicity, sex, metropolitan residence, cancer type, and stage at diagnosis. Results: A total of 42,970 children with cancer were included. Overall, there were increases in 2-year survival among children in expansion states (90.5% in 2011-2013 to 91.4% in 2014-2017) but no change among children in non-expansion states (90.0% in 2011-2013 to 90.0% in 2014-2017). In adjusted difference-in-differences analyses, there was no significant change in survival after Medicaid expansion for children in expansion vs. non-expansion states (1.01 percentage points, 95% CI = -0.23 to 2.25, p = 0.11). In difference-in-differences analyses by race/ethnicity, there was a significant expansion-associated improvement in survival in Black children (3.97 percentage points, 95% CI = 0.02 to 7.93, p = 0.049) but not in White children (0.4 percentage points, 95% CI = -1.07 to 2.04, p = 0.54). There were also expansion-associated improvements in survival among children residing in counties with the lowest quartile of county income (5.88 percentage points, 95% CI = 0.38 to 11.38, p = 0.036) but not for those in higher income counties (1.15, 1.23, and 0.12 percentage points for 2nd, 3rd, and 4th quartiles, respectively). Conclusions: Medicaid expansion, through presumed increases in Medicaid coverage via welcome mat effects, was associated with increased 2-year survival for Black children and children residing in low-income counties. However, the concentration of Black children in states that have not expanded Medicaid highlights the need for further advocacy to more fully achieve improved outcomes. Future data are needed to clarify potential long-term impacts of Medicaid expansion on childhood cancer outcomes.
Associations between interpersonal violence and cancer risk factors for transgender and cisgender people.
Authors: Alpert Ash B. , Sayegh Sabrina Jamileh , Strawderman Myla S. , Cunliffe Scott , Cupertino Ana Paula , Griggs Jennifer J. , Cerulli Catherine 
Published: June 2022

6516 Background: Cancer risk factors for transgender people are largely unexplored. Extreme rates of interpersonal violence experienced by transgender people may increase the risk of cancer. The associations between exposure to interpersonal violence and cancer risk factors have not been investigated. Methods: We searched for experiences of violence in cohorts of 923 transgender and 1846 cisgender people matched by age, follow-up time, and year of the first encounter and measured the association between these experiences and smoking as well as BMI ≥ 40. We then estimated the prevalence ratios for these risk factors using robust Poisson regression models including gender identity, violence, and their interaction, adjusted for age and follow-up time. Results: Transgender people experienced more violence than cisgender people. Among transgender people, there were significantly higher rates of smoking among those who had experienced any type of violence (50% vs 35%, p<.0001) and borderline significantly higher rates of BMI ≥ 40 (23% vs 18%, p=.05). Among cisgender people, significantly higher rates of smoking in those who had experienced violence (52% vs 31%, p<.0001) and significantly higher rates of BMI ≥ 40 (23% vs 11%, p<0.001) were also demonstrated. No statistically significant difference was demonstrated in the association between violence and smoking in transgender compared with cisgender people (prevalence ratio (PR).87, p=.17). A statistically significant difference was demonstrated in the association between violence and BMI ≥ 40 in transgender compared to cisgender people (PR.65, p=.02). Conclusions: Given the association between violence and cancer risk factors, eliminating violence is of profound concern to the oncology community. Violence across the life course is markedly higher in transgender versus cisgender people. Interventions are urgently needed to eliminate violence. Cancer prevention research should investigate the efficacy of methodologies known to impact interpersonal violence, including those modifying structural factors to decrease socioeconomic disparities, stigma, and oppression. [Table: see text]
Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) as intermediate endpoints for survival in metastatic breast cancer: A real-world experience.
Authors: Labaki Chris , Bakouny Ziad , Sanglier Thibaut , Schmidt Andrew Lachlan , Shim Jinjoo , Braun David A. , Bouquet Fanny , Joyce Maureen Ann , Xie Wanling , Tolaney Sara M. , Choueiri Toni K. 
Published: June 2022

6520 Background: Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) are two endpoints of clinical interest in patients with metastatic breast cancer (MBC). Their validation as intermediate endpoints for overall survival (OS), in a real-world setting, remains not fully established. Methods: We conducted a retrospective cohort study using the nationwide US Electronic Health Record-derived de-identified Flatiron Health database. The study population included pts diagnosed with MBC from Jan 1, 2011 to Feb 30, 2021. rwPFS was defined as the time from start of first-line systemic therapy for MBC to disease progression or death. TTNT was defined as the time from start of first-line systemic therapy until start of next line of therapy. The nonparametric Kendall tau correlation between each surrogate endpoint (rwPFS and TTNT) and OS was evaluated using the Hougaard copula model in the Weibull margin distribution. Kendall’s tau (τ) with its 95%CI was calculated across the entire dataset, and within each disease subgroup defined by receptor (ER and/or PR status defined as hormone receptor [HR], and HER2) status. This work was conducted on behalf of the imCORE network and the Dana-Farber Cancer Institute. Results: Overall, 9,770 patients with MBC were included. Median age was 63 years (IQR: 54-72 years). HR+/HER2- disease represented the most frequent MBC subtype (n=6,287; 64.4%), followed by HER2+ (n=2,096; 21.5%) and triple negative (n=1,387; 14.2%) disease. Median f/u was 41.5 months (95%CI: 40.4 to 42.8). Median OS in the overall population was 32.4 months (95%CI: 31.2 to 33.3). Median rwPFS was 11.5 months (95%CI: 11.1 to 11.9), and median TTNT was 11.1 months (95%CI: 10.7 to 11.5). Across the entire population, the correlation of rwPFS with OS was 0.54 (95%CI: 0.53-0.56), while the correlation of TTNT with OS was 0.47 (95%CI: 0.46-0.48) (Table). Conclusions: rwPFS and TTNT may represent meaningful intermediate endpoints for OS in patients with MBC overall, and within the different disease subgroups. [Table: see text]
Overall cancer survival inequalities in the state of São Paulo: A comparison between public and private systems.
Authors: Teixeira Bruno Casaes , Rider Alex , Holbrook Tim , Piercy James , Lux Michael Patrick 
Published: June 2022

6525 Background: Brazilian cancer patients under the public healthcare system receive diagnoses and treatment at a later disease stage on average than private patients, likely due to the public system having less access than the private system to treatment and diagnostic technologies. The impact of the different healthcare systems on survival is unknown. We aimed to evaluate the difference in overall survival (OS) in cancer patients under public vs. private healthcare systems in São Paulo, Brazil. Methods: Data were drawn from the hospital-based cancer registry of the Fundação Oncocentro de São Paulo capturing clinical and demographic data including clinical setting (private/public), date of diagnosis, and disease stage. All patients had complete medical records and malignant, well classified tumors. Analyses used Cox proportional hazards regressions. For multivariate (MTV) and propensity score matched (PSM) analyses; tumor topology and morphology, patient demographics and diagnostic care setting were used as covariates. Analyses were performed for overall cancers and for 20 separate tumor types as recommended by the National Institute of Cancer. Results: Data from 189,850 patients were analyzed. For all cancers, the hazard ratio (HR) for OS for public vs. private healthcare was 2.30 (CI 95% 2.20 - 2.39) in univariate (UNV), 1.59 (CI 95% 1.52 - 1.66) in MTV and 1.69 (CI 95% 1.61 - 1.77) in PSM, indicating that patients under the public system were between 2.30 and 1.69 times less likely to survive their cancer (Table 1). The cancer type with the biggest HR using PSM was multiple myeloma (HR 2.37 CI95% 1.82 - 3.08). Conclusions: Our results show Brazilian cancer patients under the public healthcare system were in some cases more than twice as likely to die from cancer than private patients. Despite possible differences between these populations in lifestyle and other potential influencing factors, our results most likely reflect differences between the two systems in access to treatment and diagnostic technologies. Our findings highlight the inequality of care in public vs. private healthcare in Brazil. Focus should be on closing the gap between the two systems in cancer diagnosis and treatment.[Table: see text]