bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrotinib-based therapy for patients with HER2-positive breast cancer: A multicenter, real-world study.
Authors: Wang Haoqi , Liu Yueping , Yang Hua , Wang Shuaibing , Cui Guozhong , Ma Jie , Liu Yunjiang , Li Xianqiao , Luo Ruizhen , Zhang Wei , Geng Cuizhi 
Published: June 2022

1040 Background: Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for the treatment of HER2-positive advanced breast cancer in China. Real-world data is instructive for effect evaluation and application of the drug in clinical practice. Herein, this study was conducted to evaluate the effectiveness and safety of pyrotinib-based therapy in patients with HER2-positive breast cancer in the real-world setting. Methods: In this retrospective, multicenter, real-world study, data of patients with HER2-positive breast cancer who received pyrotinib-based therapy from 19 sites were reviewed. Disease characteristics, prior therapies, and treatment patterns were summarized. Progression-free survival (PFS) and the incidence of diarrhea were analyzed. Results: Between September 2018 and June 2021, a total of 378 patients with HER2-positive advanced breast cancer were included. Of 378 patients, 47.4% had hormone receptor (HR)-positive disease, 41.3% had HR-negative disease, and 11.4% had unknown HR status. Brain, lung, liver, and bone metastases were found in 24.9%, 35.7%, 31.7%, and 33.1% of all cases, respectively. Most of patients (83.1%) were trastuzumab-exposed, 12.7% were pertuzumab-exposed, and 8.2% had been treated with lapatinib or neratinib before receiving pyrotinib. Pyrotinib plus chemotherapy (211 [55.8%]) was the most commonly used regimen, followed by pyrotinib monotherapy (115 [30.4%]), pyrotinib plus trastuzumab and chemotherapy (29 [7.7%]), other regimens (18 [4.8%]), and unknown regimen (5 [1.3%]). Standard dose (400 mg once daily) was used in 256 (67.7%) patients. With a median follow-up duration of 20.5 months, the median PFS was 13.0 months (95%CI, 12.0-14.0). Further analyses showed that the median PFS did not differ in subgroups by age (≥65 or < 65 years), HR status (positive or negative), brain metastasis (yes or no), lung metastasis (yes or no), liver metastasis (yes or no), bone metastasis (yes or no), prior exposure to trastuzumab (yes or no), treatment regimen (pyrotinib monotherapy or combination therapy). Significant variance was discovered between sufficient dosage group and non-sufficient group (13.2 months vs 10.93 months, p= 0.028). The survival advantage of sufficient dosage was also evident in brain metastasis cases (14.4 months vs 8.3 months, p= 0.043).The most common adverse event was diarrhea (85.7%), and grade ≥3 diarrhea occurred in 18.5% of patients. Diarrhea was the leading cause for does reduction of pyrotinib. Conclusions: The PFS data in our study was similar to previous clinical trials referring to HER2-positive advanced breast cancer treated with pyrotinib. Cases with brain metastasis also displayed a satisfactory survival result. Sufficient dosage is of great importance for prolonged survival, prevention of diarrhea may efficiently avoid does reduction and guarantee the drug efficacy.
Factors associated with short- and long-term survival in metastatic HER2+ breast cancer.
Authors: Leone Jose Pablo , Leone Julieta , Vallejo Carlos Teodoro , Parsons Heather Anne , Hassett Michael J. , Lin Nancy U. 
Published: June 2022

1047 Background: There have been significant therapeutic advances for HER2+ metastatic breast cancer (MBC) over the past decade. The aim of this study was to evaluate prognostic factors in metastatic HER2+ disease and their relationship with short- and long-term overall survival (OS) in the modern era. Methods: We evaluated patients (pts) with de novo metastatic HER2+ breast cancer diagnosed between years (y) 2010 and 2018, reported in SEER. Univariate analyses were performed to determine the effect of each variable on OS. Significant variables were included in a multivariate Cox model for OS that evaluated all pts diagnosed 2010 – 2018. Univariate and multivariate logistic regression was used to evaluate the association of each variable with short (< 2 y) and long (≥ 5 y) term OS. To allow sufficient follow up, only pts diagnosed 2010 – 2016 were included in the logistic regression for OS < 2 y, and only those diagnosed 2010 – 2014 were included for OS ≥ 5 y. Results: We included 5,576 pts with a median follow up of 48 months (IQR 25 – 73 months). Median OS was 41 months. The proportion alive at 2 y, 5 y, and 8 y, was 63.3% (95% CI 62.0% - 64.7%), 37.8% (95% CI 36.2% - 39.4%) and 26.8% (95% CI 24.8% - 28.9%), respectively. In multivariate analysis for OS, older vs younger age (HR 2.5), black vs white pts (HR 1.4), non-ductal non-lobular vs ductal (HR 2.7), bone metastases vs not (HR 1.2), brain metastases vs not (HR 1.8), liver metastases vs not (HR 1.6), lung metastases vs not (HR 1.3), 6 metastatic organ sites vs 1 (HR 3.6), ER/PR- vs + (HR 1.3), < $35k income vs ≥ $75k (HR 1.8), and being diagnosed in earlier years (HR 1.06 per each prior year) had significantly worse OS (all p≤0.044). Similar results were seen for breast cancer-specific survival. Factors associated with < 2 y OS in adjusted models were older age (OR 3.8), black race (OR 1.5), non-ductal non-lobular (OR 4.6), brain metastases (OR 3.0), liver metastases (OR 2.0), lung metastases (OR 1.6), ER/PR- (OR 1.7) and lower income (OR 1.6), all p < 0.04. Number of metastatic organ sites was not significant in this model. Factors associated with ≥ 5 y OS in adjusted models were younger age (OR 2.9), white vs black race (OR 1.7), fewer metastatic organ sites (OR 2.6), ER/PR+ (OR 1.3), and higher income (OR 3.3), all p < 0.02. Specific organ sites (bone, brain, liver and lung) were not significant in this model. Conclusions: In this cohort of pts with de novo HER2+ MBC, OS improved significantly over the study period, and a considerable proportion of pts were still alive at 8 y. Factors associated with shorter survival included older age, black race, lower income, and the presence of visceral or brain metastases. Long-term (≥ 5 y) survival was associated with both demographic (younger age, white race, higher income) and tumor-related (fewer metastatic sites, ER/PR positivity) factors.
Mutation spectrum and rates of variants of uncertain significance among African American males undergoing prostate cancer germline testing: Need for equity in genetic testing.
Authors: Giri Veda N. , Hartman Rebecca L. , Pritzlaff Mary , Keith Scott W. 
Published: June 2022

10502 Background: Germline testing (GT) for prostate cancer (PCA) is central to metastatic disease management, PCA screening strategies, and hereditary cancer assessment. African American (AA) males have a higher burden of PCA, yet have lower engagement in germline testing which limits understanding of genetic contribution to PCA. Here we evaluated the germline spectrum of AA and White males with PCA undergoing clinical multigene panel testing (MGPT) to inform germline testing strategies with attention to equity. Methods: Study participants included AA men and White men with PCA who underwent a 14-gene MGPT between April 2012 - December 2020 at a clinical diagnostic laboratory (Ambry Genetics). Exclusions were men with known pathogenic variants reported in their families or who had prior genetic testing. MGPT included: ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, TP53. Sanger or next generation sequencing analysis was performed per standard clinical testing protocol. Variant classification was per ACMG 5-tier system. Descriptive statistics summarized results with counts and percentages for categorical variables and mean and standard deviation for continuous variables. Data were compared with Fisher’s exact, Chi-squared, two proportion z-test, or two sample t-test, as appropriate. Significance level was set a priori at 0.05. Results: The dataset included genetic and clinical data from 427 males who had undergone MGPT: White males (n = 190; 45.5%) and AA males (n = 237; 55.5%). Mean age at diagnosis was 59 + 9.3 years. Among men whose Gleason score was indicated (72%), 47% had Gleason > = 8. Majority of men indicated having a 1st/2nd degree relative with PCA (68.97%) or 1st/2nd degree relative with any cancer (99.2%). In the entire cohort, 8.2% tested positive for a pathogenic/likely pathogenic variant; AA males (n = 14, 5.91%) and White males (n = 21, 11.05%). VUS only was reported in 21.31% of the overall cohort with a significant difference noted between AA and White males (25.32% vs. 16.32%, respectively; p = 0.0238). Mutation spectrum in AA males included: BRCA2 (n = 7), PALB2 (n = 3), ATM (n = 3), and BRCA1 (n = 1). Among White males, a wider spectrum of mutations was observed: BRCA2 (n = 6), ATM (n = 5), HOXB13 (n = 5), CHEK2 (n = 2), TP53 (n = 1), and NBN (n = 2). The proportion of AA males with multiple VUS was significantly higher than for Caucasian males (5.1% vs. 0.53%, p = 0.003). Conclusions: Clinical germline testing among AA males reveals a narrow spectrum of mutations in key DNA repair genes, with important implications for precision therapy and hereditary cancer assessment. Furthermore, AA males had significantly higher rates of multiple VUS, indicating critical need for greater inclusion of diverse populations in genetic studies to discern the pathogenic spectrum contributing to PCA aggressiveness and risk.
Implementing systematized patient-facing Lynch syndrome (LS) risk assessment in oncology using the electronic health record (EHR) system.
Authors: Ukaegbu Chinedu , Yurgelun Matthew B. , Caruso Alyson , McAuliffe Leanne , Chittenden Anu B. , Whittaker Sarah , Cleveland Jessica , Black Brittany , Zhang Sunyi , Hassett Michael J. , McCleary Nadine Jackson , Syngal Sapna 
Published: June 2022

10503 Background: Lynch syndrome (LS) is the most common inherited cause of colorectal (CRC) and endometrial cancers. Significant provider and institutional level barriers limit LS detection, even in oncology patients with LS-associated cancers. PREMM5 is a validated tool based on personal and family cancer history that is recommended by national professional societies for LS risk assessment. This project’s goal was to study the feasibility of patient-facing LS risk assessment using a PREMM5 screener embedded in an electronic health record (EHR) system, as a means of improving LS identification. Methods: The PREMM5 LS screener intake questions were adapted to be completed by patients rather than healthcare providers. Screener adaptation and implementation involved iterative review by multidisciplinary experts and multilevel stakeholder engagement. The patient-facing PREMM5 LS screener was embedded in the EHR (Epic) at the Dana-Farber Cancer Institute (DFCI) to enable remote (via the EHR patient portal) and on-site completion (in clinic waiting rooms). All new gastrointestinal (GI) cancer patients seen at DFCI for initial oncology consultation from 6/2020-12/2021 were invited through the portal to complete the screener. PREMM5 scores ≥2.5% were considered “positive”, with genetics referral recommended. Beginning 2/2021, the EHR generated an automated provider-facing alert for positive screens. Results: 35% (1504/4262) of new GI cancer patients completed the screener. 367/1504 (24%) had a positive PREMM5 screen (mean age 53 years), of whom 66% were male, and 62%, 12% and 10% had CRC, neuroendocrine and pancreas cancer respectively. 97% (357/367) of screen positives completed the PREMM5 screener remotely through the portal. 102/367 (28%) received a genetics referral as a result of their positive PREMM5 screen (not including 75 genetics referrals outside this workflow), 13 of whom had a pathogenic variant (PV) on germline testing, including 4 with LS ( MSH2, MSH6, PMS2), and others with PVs in ATM, BRCA2, CHEK2, NTHL1, RAD50 and RECQL4. Conclusions: A practice-wide patient-facing EHR-integrated PREMM5 risk assessment workflow is feasible and identified nearly 1 in 4 general GI oncology patients as warranting genetic evaluation, resulting in the identification of numerous actionable germline PVs. This method of deployment could make genetic risk assessment more accessible to non-genetics providers. The suboptimal screener completion rate and 28% genetics referral rate among positive screens suggest the need for additional refinements, including patient and provider engagement and outreach to positive screens who do not follow up with appointments for genetic evaluation.
Effect of lung cancer screening on the incidence of advanced lung cancer in the United States: A SEER database analysis.
Authors: Akanbi Maxwell Oluwole , Adekolujo Orimisan Samuel , Isaac Dan , Wahab Ahsan , Wang Ling , Hrinczenko Borys 
Published: June 2022

10506 Background: In 2013, the USPSTF recommended screening for lung cancer with low-dose chest computed tomography (LDCT). This was based on the results of the National Lung Screening Trial which showed a 20% relative reduction in mortality from LDCT compared with chest radiography. In Feb/March 2015, the Centers for Medicare and Medicaid (CMS) provided screening guidelines and they and private insurers started covering the cost of LDCT. The impact of this recommendation in the real-world setting is unknown. We investigated the impact of LDCT recommendations on the incidence of advanced lung cancer (a-LCa) in the US general population. We sought to verify that the implementation of LDCT will yield an earlier lung cancer diagnosis and thereby reduce the incidence of later stages of lung cancer. Methods: From the Surveillance, Epidemiology, and End Results (SEER) 18 registries database, we identified adults 55-80 years diagnosed with regional or metastatic (advanced) lung cancer from 2004 to 2018. Age-adjusted incidence rates (AAIR) of advanced lung cancer in 2004-2014 (Pre-LDCT) and 2015-2018 (Post-LDCT) were compared using interrupted time series (ITS) regression analyses. Analyses were stratified by sex, race, and residence. Results: A total of 400,343 patients who met the study criteria were included. Of these, 219,828 (55%) were women and 76% (n = 304,801) were non-Hispanic White. At all periods, the AAIR of a-LCa was highest in non-Hispanic Blacks. Overall, there was a 41% decline in the AAIR of a-LCa in the post-LDCT period compared to the pre-LDCT era (Annual decline of 7.6 vs 4.5 /100,000 person-years (PY) for 2015-2018 vs 2004-2014, p < 0.01). Women experienced a more accelerated decline in the AAIR of a-LCa compared to men (53% versus 30%). By race, the annual rates of a-LCa declined most rapidly among non-Hispanic Blacks (55%, 9.5/ 100,000 PY, 2015-2018 vs 4.7/100,000 PY, 2004-2014, p < 0.01), and the slowest rate of decline was among Hispanics (41%, 4.6/100,000 PY,2015-2018 vs 2.7/100,000 PY, 2004-2014, p < 0.01). By residence, non-metropolitan dwellers experienced a greater decline in annual rates of a-LCa compared with metropolitan dwellers (non-Metropolitan: 69%, 10.1/100,000 PY, 2015-2018 vs 3.2/100,000 PY 2003-2014, p < 0.01: Metropolitan dwellers: 37%, 7.2/100,000 PY 2015-2018 vs 4.5/100,000 PY, p < 0.01). Conclusions: Using population-based data we found a significant decline in rates of a-LCa following the adoption of LDCT for lung cancer screening in the US. Rates of decline in the incidence of a-LCa, however, varied among subgroups. Non-Hispanic Blacks, women, and rural dwellers experienced the most decline in annual rates of a-LCa from 2015 to 2018. Our study shows the overall benefit of LDCT in marginalized communities. However, the impact of our findings on lung cancer mortality will still need further study.
Germline mutational landscape of non-highly penetrant Fanconi anemia genes unveiled from sequencing of 5,044 patients with solid tumor cancer.
Authors: McDonnell Kevin , Hong Christine , Bonner Joseph D. , Lindsey Sidney Smith , Solomon Ilana , Hampel Heather , Park Wai , Idos Gregory , Gray Stacy W. , Gruber Stephen B. 
Published: June 2022

10521 Background: Nearly two dozen Fanconi anemia (FA) genes work in concert to mediate critical DNA repair steps. Previous investigations have well described germline pathogenic variation and associated solid tumor cancer predisposition in the highly penetrant (HP)-FA genes, BRCA1 (FANCS), BRCA2 (FANCD1) and PALB2 (FANCN). To date, understanding of pathogenic variation and cancer association among non-HP-FA genes remains incomplete. In this study we investigated the germline mutational landscape of non-HP-FA genes in patients with a personal/family history of a solid tumor. Methods: Unselected, consented patients with a personal/personal history of solid tumor cancer underwent germline testing through a sponsored program of universal access. Testing used a custom panel to detect pathogenic single nucleotide variants, short insertions/deletions and exon-level deletions/duplications of 155 cancer-predisposition genes including 15 non-HP-FA genes [ FANCA, FANCB, FANCC, FAND2, FANCE, FANCF, FANCG, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCO (RAD51C), FANCP (SLX4), FANCQ (ERCC4) and FANCU (XRCC2)]. Here we summarize germline pathogenic variant frequency in non-HP-FA genes and describe the mutational landscape across solid tumors. Additionally, we report the clinical actionability (on- and off-label FDA approved drug availability and/or clinical trial eligibility) of identified variants. Results: 5044 patients consented and completed germline genetic testing. 1014/5044 (20.1%) of patients carried a pathogenic variant in a cancer predisposition gene. 116/1014 (11.4%) of germline positive patients carried a pathogenic variant in a non-HP-FA gene. Non-HP-FA genes with highest frequencies included: FANCA (28 patients), FANCM (19 patients), BRIP1 (FANCJ) (19 patents) and FANCC (14 patients). Testing identified germline non-HP-FA pathogenic variants in eighteen different tumor types. The tumor types associated with the highest percentages of associated germline non-HP-FA pathogenic variants included: squamous cell cancers (8.2%), bladder/urothelial cancer (5.0%), breast cancer (3.5%) and ovarian/fallopian tube cancers (3.5%). Moreover, 19 patients carrying a non-HP-FA germline pathogenic variant qualified for an on- or off-label FDA-approved drug; 101 patients achieved clinical trial eligibility by virtue of their non-HP-FA variant. Conclusions: Our study offers a landscape view of germline pathogenic variants in non-HP-FA genes in patients with a history of a solid tumor. Furthermore, this investigation provides a basis for further examination of associations between these germline pathogenic variants and solid tumor cancer predisposition. Finally, importantly, our work underscores the value of expanded germline non-HP-FA gene testing to optimize therapeutic and clinical trial opportunities for cancer patients.
Cost-effectiveness of targeted genomic risk provision to prevent skin cancer: Results of a randomized trial.
Authors: Law Chi Kin , Smit Amelia K , Cust Anne E. , Trevena Lyndal , Penas Pablo Fernandez , Nieweg Omgo E. , Menzies Alexander M. , Wordsworth Sarah , Morton Rachael L. 
Published: June 2022

10536 Background: Many melanomas and keratinocyte cancers (KC) are preventable by reducing sun exposure and improving sun protection behaviors. Recent evidence indicates a melanoma prevention program involving personalized genomic risk information provision can reduce self-reported sunburns at 12 months in Australian adults with no history of melanoma. This was alongside genetic counselling and educational materials on skin cancer prevention and early detection. However, the economic impact of this approach was unclear. This study aimed to determine the cost-effectiveness of the program to prevent melanoma and KC. Methods: A decision-analytic Markov model was developed to simulate the lifetime cost-effectiveness of personalized genomic risk provision compared with standard prevention advice alone, from a health system perspective. We used data from the Melanoma Genomics Managing Your Risk Study Randomized Control Trial. Traditional risk was measured by a validated melanoma risk prediction model involving hair color, nevus density, history of non-melanoma skin cancer, family history of melanoma, level of sunbed sessions. Quality-adjusted life years (QALY) gained was the primary outcome measure used to estimate an incremental cost-effectiveness ratio (ICER). Both deterministic and probabilistic sensitivity analyses (PSA) were undertaken. Results: The cost of the genomic testing and risk counselling program was AUD$189 (USD$132) per participant. Genomic risk provision targeting high-traditional risk individuals was the most cost-effective lifetime strategy with an ICER of AUD$23,033 (USD$16,059) per QALY gained and an 80% probability of being cost-effective at a willingness-to-pay threshold of AUD$50,000, compared with standard preventive advice (Table). When genomic risk provision was extended to low-traditional risk groups the ICER was $43,746 (USD30,500) per QALY gained with a 45% probability of being cost-effective. Conclusions: Genomic risk provision targeted to individuals at high-traditional risk of melanoma is a cost-effective strategy for the prevention of melanoma and KCs. Long-term sustainability of the program’s effect should be examined in future research. Clinical trial information: ACTRN12617000691347. [Table: see text]
Increasing primary care utilization prior to cancer diagnosis in association with cancer mortality.
Authors: Qiao Edmund Men , Guram Kripa , Kotha Nikhil V. , Voora Rohith S. , Qian Alexander , Ahn Grace S. , Kalavacherla Sandhya , Pindus Ramona , Stewart Tyler F. , Banegas Matthew P. , Murphy James Don , Rose Brent S. 
Published: June 2022

10548 Background: Primary care physicians (PCPs) are significant contributors of early cancer detection yet few studies have investigated whether consistent primary care translates to improved downstream outcomes. We evaluated the impact of prior PCP utilization on metastatic disease at diagnosis and cancer-specific mortality (CSM) for a general cancer cohort and 12 tumor subtypes. Methods: We identified cancer patients ≥40 years, diagnosed from 2004-2017 within the Veterans Health Administration. For our 5-year pre-diagnostic period, we binned PCP visits into none (0 visits), some (1-4), and annual (5). Multivariable logistic regression assessed the effect of PCP utilization on metastatic disease at diagnosis and Fine-Gray regression with non-cancer death as a competing event evaluated their effect on cancer-specific mortality (CSM). These were repeated for each subtype. Results: Among 245,425 patients, mean age was 66 years with 5.7-year median follow-up. Compared with 0 visits, some PCP utilization was associated with 26% reduced odds of metastatic disease at diagnosis (odds ratio (OR), 95% confidence interval (CI): 0.74 [0.71-0.76] P<0.01) and 12% lower risk of CSM (hazard ratio (HR), 95% CI: 0.88 [0.86-0.89] P<0.01). Annual PCP utilization was associated with 39% reduced odds of metastatic disease (OR, 95% CI: 0.61 [0.59-0.63] P<0.01) and 21% lower risk of CSM (HR, 95% CI: 0.79 [0.77-0.81] P<0.01). Among subtypes, prostate cancer had the largest effect size for PCP utilization on metastatic disease at diagnosis (ORannual, 95% CI: 0.32 [0.30-0.35] P<0.01) and CSM (HRannual, 95% CI: 0.51 [0.48-0.55] P<0.01). Pancreas cancer had the lowest effect size on metastatic disease at diagnosis (ORannual, 95% CI: 0.87 [0.73-1.04] P: 0.12) and CSM (HRannual, 95% CI: 0.89 [0.82-0.97] P<0.01). The table displays additional subtypes. Conclusions: Increased PCP utilization prior to cancer diagnosis is associated with a significant decrease in metastatic disease at diagnosis and CSM, with annual utilization associated with the greatest decrease. These results are consistent when stratifying by tumor subtype. Consistent primary care must be emphasized for patients at risk of cancer. [Table: see text]