bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of socioeconomic status as measured by Neighborhood Deprivation Index on survival in metastatic breast cancer.
Authors: Puthanmadhom Narayanan Susrutha , Rosenzweig Margaret Q. , Ren Dianxu , Oesterreich Steffi , Lee Adrian V. , Brufsky Adam
Published: June 2022

1013

Background: Socioeconomic status (SES) and race are major determinants of health outcomes in the United States. We aim to assess the effect of SES as measured by the Neighborhood Deprivation Index (NDI) and race on outcomes in metastatic breast cancer patients at our center. Methods: The NDI scores for patients with metastatic breast cancer who were treated at our center between 2000 and 2017 were obtained from the Neighborhood Atlas using their Zip-Code (N = 1246). The SES groups were defined as low deprivation with an NDI score in the bottom tertile and high deprivation with NDI in the top or middle tertiles. Baseline characteristics were compared between the SES groups with Bonferroni correction. Univariate and multivariate survival analysis were performed using the R packages “survival” and “survminer”. Results: Race was the only baseline characteristic that was significantly different between the SES groups, the high deprivation group had a higher proportion of African Americans (10.5%) than the low deprivation group (3.7%, P = 9.3e-05). In univariate Kaplan-Meier survival analysis, both SES and race had significant effect on overall survival such that the high deprivation group had worse survival than low deprivation (Log Rank P = 0.01) and African Americans had worse survival than Caucasians (P = 0.008). In multivariate Cox proportional hazard model, SES, but not race, had a significant effect on overall survival (hazard ratio for high deprivation was 1.19 [95% Confidence interval 1.04 - 1.37], P = 0.01; Table). Progression-free survival on first-line chemotherapy was not different between the SES groups or racial groups in both univariate and multivariate analysis. Conclusions: The current study shows that patients from the high deprivation group (i.e., low SES), have worse survival in metastatic breast cancer. Race was no longer a significant predictor of survival when SES was accounted for in the analysis. This possibly suggests that poor outcomes in the African American population is explained by the association between low SES and African American race. Based on these results, there is an urgent need for healthcare investments in the low SES neighborhoods. [Table: see text]
Increasing Black patient participation in metastatic breast cancer clinical trials: The BECOME (Black Experience of Clinical Trials and Opportunities for Meaningful Engagement) project.
Authors: Walker Stephanie , Carlson Martha , White Carol B. , Howell John , Felder Tisha M.
Published: June 2022

1014

Background: Among U.S. racial/ethnic groups, Black people with breast cancer have the highest death rate and shortest survival. Although ̃15% of cancer patients in the U.S. are Black, only 4-6% of clinical trial participants are Black. Only when trial participants reflect the diversity of the general population can oncologists understand how a drug works across subpopulations. The objectives of the BECOME initiative are to understand barriers to trial participation by Black patients with metastatic breast cancer (MBC) and to identify actions to increase participation. Methods: BECOME is sponsored by the Metastatic Breast Cancer Alliance, a consortium of representatives from nonprofit organizations, pharmaceutical/biotech companies, and patient advocates, many of whom are living with MBC. Findings from a literature review and Key Informant interviews informed a survey of U.S. adults living with MBC. Results: Of 424 survey respondents, 102 (24%) self-identified as Black. Black respondents’ trust and satisfaction with their oncology care team were high (> 90%), and 83% of Black respondents were somewhat or very likely to consider trial participation. However, 40% of Black respondents reported no one on their care team had discussed trials. Black respondents’ reasons to not participate in a trial included concerns about side effects (73%) and effectiveness (63%). Black respondents were more likely than non-Black respondents to believe unstudied treatments may be harmful (57% vs 31%). Black respondents were less likely than non-Black respondents to indicate they trust trials (73% vs 91%) and trust that people of all races/ethnicities get fair treatment in trials (32% vs 56%). Black respondents were more likely than non-Black respondents to value receiving trial information from someone with the same racial/ethnic identity (67% vs 10%), who has had breast cancer (73% vs 44%) or MBC (73% vs 51%), or who has been in a trial (72% vs 48%). Black respondents were also more likely to be motivated to participate to ensure people with their racial or ethnic identity will benefit (83% vs 51%). Conclusions: Black patients with MBC are willing to consider participating in clinical trials. Actionable steps to increase Black patient participation include: 1) enhancing awareness about trials by informing patients, increasing education, training healthcare providers to deliver patient-friendly information in an unbiased manner, and providing messaging from people of shared racial/ethnic identity and health experience; 2) building trust through clear communication; 3) addressing concerns about side effects, effectiveness, harm, and fair treatment; and 4) helping patients find and access trials. All stakeholder groups have a role to play in increasing Black patient participation in MBC clinical trials.
Detection of presumed germline pathogenic variants of hereditary breast cancer predisposition genes in circulating tumor DNA: SCRUM-Japan MONSTAR-SCREEN.
Authors: Hattori Masaya , Naito Yoichi , Yamanaka Takashi , Yasojima Hiroyuki , Nakamura Rikiya , Watanabe Junichiro , Yoshinami Tetsuhiro , Ozaki Yukinori , Fujisawa Takao , Nakamura Yoshiaki , Bando Hideaki , Yoshino Takayuki , Yamaguchi Rui , Imoto Issei , Iwata Hiroji
Published: June 2022

1029

Background: Approximately 5-10% of breast cancer are hereditary. Variant allele frequency (VAF) of hereditary breast cancer predisposition genes in circulating tumor DNA (ctDNA) may be useful for detecting presumed germline pathogenic variants. Methods: One hundred and sixty-eight patients with advanced breast cancer (ABC) who underwent ctDNA and tumor tissue sequencing analyses in the SCRUM-Japan MONSTAR-SCREEN, a cancer genome screening project in Japan, from December 2019 to November 2021 were included. The patients were tested and monitored for their genomic alterations by FoundationOne Liquid assay or FoundationOne Liquid CDx assay. The pathogenic variants (PV) of hereditary breast cancer predisposition genes with VAF of 30% or higher in ctDNA were defined as PGPV. The VAF of BRCA1/2 on ctDNA analyses in BRCA1/2 germline pathogenic variant (GPV) carriers and the prevalence of PGPV in five hereditary breast cancer predisposition genes, including ATM, BRCA1, BRCA2, CHEK2, and PALB2, were investigated. Results: From 168 patients with ABC, including 115 Luminal, 32 HER2-positive, and 21 triple negative breast cancer, with a median age of 58 years, 39 PVs in 5 genes were identified with a median VAF of 0.62% (range: 0.1-84.77). ctDNA identified GPV of known BRCA1/2 GPV carriers (1 with BRCA1 and 6 with BRCA2) , with a median VAF of 51.4% (range: 48.2-77.5). The VAF of GPV on ctDNA were higher than 30% in subsequent consecutive samples. Among 161 patients with ABC, excluding 7 known BRCA1/2 GPV carriers, 6 PGPV (1 with BRCA1, 3 with BRCA2, and 2 with PALB2) were detected, with a median VAF of 65.5% (range: 51.2-84.8). Subsequent confirmatory tests were performed for two PGPV, and the variants were confirmed to be of germline origin. Conclusions: VAF on ctDNA analysis can help to easily detect PGPV of hereditary breast cancer predisposition genes. The PGPV detected in ctDNA analysis should be validated by established germline tests, and the results could provide opportunities for targeted therapies, as well as cancer risk assessment of patients and their relatives.
Pyrotinib in combination with metronomic oral vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy: A single-center, single-arm, prospective phase 2 study.
Authors: Hao Chunfang , Wang Xu , Shi Yehui , Tong Zhongsheng , Li Shufen , Liu Xiaodong , Zhang Lan
Published: June 2022

1033

Background: In 15% to 30% of breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed, this is related to aggressive disease and poor prognosis. Although important clinical benefits for patients have been achieved by the use of the HER2 antibody trastuzumab, 50% to 74% of patients with metastatic disease have no response to treatment, and approximately 75% progress within one year. The purpose of this study was to evaluate the efficacy and safety of oral pyrotinib in combination with oral metronomic vinorelbine in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. Methods: This prospective phase 2 study enrolled patients aged 18-75 years with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy, and had an Eastern Cooperative Oncology Group performance score of 0-2. Patients received pyrotinib 400 mg once daily and vinorelbine 40 mg once on Monday, Wednesday, Friday of each week until disease progression or unacceptable toxicity. Both pyrotinib and vinorelbine were orally administered 30 min after meals. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease remission rate (DCR), overall survival (OS), quality of life (QoL) and safety (CTCAE 5.0). The follow-up of this study is ongoing, but enrolment is closed. This study is registered on Clinical Trials.gov, number NCT04903652. Results: Between Oct 21, 2019, and Jan 21, 2022, 36 patients were enrolled and all of them were included in the intent-to-treat (ITT) population. 20 of 36 patients had disease progress or death. Median follow-up was 16.23 months. The median PFS (mPFS) was 14.23 months (95% CI 8.13-20.33). The ORR and DCR were 38.9% and 83.3%, respectively. The median OS was not reached. Grade 3 adverse events (AEs) occurred in 17 of 36 patients, the most common were diarrhea 27.8% and stomachache 5.6%. No grade 4 AEs were observed. Conclusions: Pyrotinib combined with metronomic oral vinorelbine showed promising efficacy and manageable safety in patients with HER2-positive advanced breast cancer who had failed prior trastuzumab-based therapy. This study might represent a potential treatment option for these patients. Clinical trial information: NCT04903652..
Monitoring and management of interstitial lung disease/pneumonitis among patients with metastatic breast cancer treated with trastuzumab deruxtecan.
Authors: Kish Jonathan K. , Mehta Sandhya , Kwong Jackie , Lam Clara , Falkenstein Angelica , Brown-Bickerstaff Cherrishe , Xiao Dong , Feinberg Bruce A.
Published: June 2022

1036

Background: Trastuzumab Deruxtecan (T-DXd) was associated with an increased risk of interstitial lung disease (ILD)/pneumonitis (P) in metastatic breast cancer (mBC) patients (pts) in clinical trials, leading to ILD/P monitoring and management guidelines in the product label. This study aims to describe the monitoring and management of ILD/P during T-DXd therapy among US community oncology practices. Methods: Oncologists in the Cardinal Health Oncology Provider Extended Network (OPEN) participated in a cross-sectional survey on monitoring approaches for ILD/P among mBC pts. Participating physicians provided data from medical charts of up to 10 pts who were treated with T-DXd regarding presence of ILD/P symptoms, management, and outcomes of ILD/P symptoms. Results: Twenty-eight physicians from across the U.S participated and provided data on 149 T-DXd pts. Nearly all physicians reported they were monitoring ILD/P after T-DXd initiation by physical examination (n = 27), symptoms checklist (n = 25) and pulse oximetry (n = 23) at every visit, whereas fewer reported performing lung CT scan (n = 18), echocardiogram (n = 13), chest X-ray (n = 12), lung PET scan (n = 10), pulmonary function tests (n = 8) and diffusion testing (n = 7) on a less frequent basis. Among 149 T-DXd pts, 4 pts were diagnosed with ILD/P over an average T-DXd treatment duration of 5.5 months. All 4 cases initiated T-DXd treatment at 5.4mg/kg every 3 weeks, experienced ILD/P within the first 5 cycles of T-DXd, were diagnosed with lung CT scan and initially presented with Grade 2 symptomology (2 cases progressed to Grade 3). For both cases that remained as Grade 2, ILD/P completely resolved within 23 days. One case received IV methylprednisolone (1000mg daily; duration of therapy (DOT): 3 days) during hospitalization, oxygen therapy and T-DXd was permanently discontinued; whereas the other one received oral prednisone (started at 40mg daily and tapered to 5mg daily; DOT: 7 days) and T-DXd dose was held. For the two grade 3 cases, one received IV methylprednisolone (125mg daily; DOT: 7 days) during hospitalization, T-DXd dose was held, and ILD/P completely resolved within 11 days; whereas the other case received oral prednisone (started at 80mg daily and tapered to 5mg daily; DOT: 63 days), oxygen therapy, T-DXd was permanently discontinued, and ILD/P resolved with sequela within 46 days. Conclusions: ILD/P incidence in this small study sample of patients receiving T-DXd treatment was 2.7%. Although general awareness of ILD and routine screening by pulse oximetry and physical exam were common, management approaches for ILD/P were not always consistent with T-DXd prescribing information. Further physician education may be needed to improve appropriate management of ILD/P and outcomes for T-DXd pts.
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]
Human papillomavirus (HPV) vaccine hesitancy trends in the United States.
Authors: Adjei Boakye Eric , Abouelella Dina K , Nair Mrudula , Osazuwa-Peters Nosayaba
Published: June 2022

10550

Background: Despite the human papillomavirus (HPV) vaccine being safe and effective at preventing HPV-associated cancers, vaccine update is low. Several factors have been identified as barriers to getting the HPV vaccine. However, it is unclear if these factors have changed since vaccine licensure. Thus, we assessed trends in the top five reasons for vaccine hesitancy in the last decade in the US. Methods: We analyzed the 2010–2019 National Immunization Survey–Teen data, a national survey representative of the US adolescent population. We identified adolescents (n = 16,383) who had received zero dose of the HPV vaccine (unvaccinated adolescents). Parents of unvaccinated adolescents were asked how likely they will vaccinate their child in the next 12 months. Parents who responded with “not too likely”, “not likely at all” or “not sure/don’t know” (vaccine hesitant) were asked what the reasons are for their hesitancy. The top five most cited reasons for vaccine hesitancy: “not necessary”, “safety concerns”, “lack of recommendation”, “lack of knowledge”, and “not sexually active” were included in the study. Joinpoint regression estimated yearly increases/decreases in these reasons using annual percent changes. Results: The proportion of unvaccinated adolescents whose parents cited “safety concerns”’ as a reason for HPV vaccine hesitancy decreased from 2010 to 2012 but increased significantly from 2012 to 2019 at an average of 8.6% annually. The proportion of unvaccinated adolescents whose parents cited “not sexually active” as a reason for HPV vaccine hesitancy decreased on average by 33.1% from 2010-2012 and then at an average of 11.5% in the remaining years. The proportion of unvaccinated adolescents whose parents cited “not necessary” as a reason for HPV vaccine hesitancy decreased from 2010-2012 but significantly decreased by an average of 11.0% yearly from 2012-2019. The proportion of unvaccinated adolescents whose parents cited “lack of recommendation” and “lack of knowledge” as reasons for HPV vaccine hesitancy decreased over the 10-year period though not statistically significant. Conclusions: There was a decrease in most of the reasons cited by parents for vaccine hesitancy except vaccine safety which has been increasing from 2012 to 2019. These findings suggest an urgent need to combat the rising sentiment of safety concerns among parents of unvaccinated children to increase HPV vaccine confidence.
CDK4/6 inhibitors outcomes in patients with advanced breast cancer based on HER2-low expression.
Authors: Lapuchesky Laura Sabina , Bortz Marcos , Waisberg Federico , Enrico Diego Hernán , Bruno Luisina Ines , Ostinelli Cristian Alexis , Rivero Sergio Gabriel , Rodriguez Andres , Zarba Martin , Loza Martin , Fabiano Verónica Yamila , Amat Mora , Pombo Maria Teresa , Noro Maria Laura , Coló Federico Andrés , Chacon Reinaldo D. , Chacon Matias Rodrigo , Nadal Jorge Carlos , Nervo Adrian , Costanzo Maria Victoria
Published: June 2022

1056

Background: HER2-low expression, defined as HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization assay (FISH), accounts for 50% of breast cancers. There is limited and conflicting evidence regarding the efficacy of cyclin-dependent kinase (CDK) 4 and 6 inhibitors in patients with ER+ and HER2-low tumors. This study aimed to investigate the prognostic value of HER2-low expression in patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors. Methods: We retrospectively selected consecutive patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors plus endocrine therapy in our institution from May 2015 to Feb 2020. Two cohorts were compared, including HER2-0 (IHC score) and HER2-low (HER2 IHC score 1+ and 2+ [negative FISH]) tumors. Comparisons in progression-free survival (PFS) and overall survival (OS) were performed using a log-rank test. The prognostic value of HER2-low was investigated by the Cox regression model. Results: Among the 186 patients included, median age at treatment was 55 (r 27-84), and majority had ECOG 0 (126, 67.8%). Progesterone receptor was positive in 155 (83.3%) tumors. Of note, most patients received CDK4/6 inhibitors and endocrine therapy as first-line setting (131, 70.4%). Mostly received palbociclib (161, 86.6%), while ribociclib and abemaciclib were used in 23 (12.4%) and 2 (1.08%) patients, respectively. Overall, 27 patients (14.5%) had de novo metastatic disease, 68 (36.6%) had only bone metastases, and 69 (37.1%) had visceral disease. Of the total population, 64 (34.4%) tumors were HER2-low (43 [23.1%] HER2-1+, and 21 [11.3%] HER2-2+), and 122 (65.6%) were HER2-0. Median PFS among patients with HER2-0 and HER-low were 19 mo. (95% CI, 13.9-24.1), and 15.6 mo. (95% CI, 11.1-20.0), p = 0.074, respectively. In patients treated with CDK 4/6 in the first-line setting, no statistically significant differences were observed in terms of PFS and OS between HER2-0 and HER2-low (PFS HR 0.73 [95% CI, 0.47-1.13; p = 0.160], and OS HR 1.04 [95% CI, 0.51-2.14; p = 0.909]). Conclusions: In our study, HER2-low expression did not show a statistically significant impact on patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors. Our study supports the necessity of real-world evidence and the design of pooled analysis to understand the real implication of this biomarker in patients with ER+/HER2-negative tumors.
Patient-reported disruptions to cancer care in the U.S. during the COVID-19 pandemic: A national cross-sectional study.
Authors: Iyer Sharanya , Lang Jacob , Narendrula Aparna , Zanotti Kristine M. , Sindhwani Puneet , Mossialos Elias , Ekwenna Obi
Published: June 2022

10561

Background: Disruptions to cancer care during the COVID-19 pandemic due to disease mitigation efforts, supply-chain issues, and fear of COVID-19 have all been reported, but study of their extent has been limited. The purpose of this study is to evaluate the extent and associations with patient reported disruptions to cancer treatment and other care during the COVID-19 pandemic using nationally representative data. Methods: This cross-sectional study uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults who reported requiring current cancer treatment or other care related to their cancer in the second half of 2020 were included. Rates of patients with self-reported changes, delays, or cancellations to cancer treatment or other cancer-related care due to the COVID-19 pandemic were calculated and their associations with demographic and other variables were analyzed. All data were adjusted using sample weights and specific variables to account for stratification and other survey characteristics using the Stata svy command. Chi-square testing was used to compare proportions across variable groups. Univariable logistic regression analysis was utilized to assess variable associations with change, delay, or cancellations to cancer care during the COVID-19 pandemic. Multivariable logistic regression analysis was used to create a model adjusted for select demographic variables. Results: A sample-weighted 2,867,326 adults (n=574) reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. Of these, 189 (32.1%) reported any change, delay, or cancellation due to the pandemic. On univariable analysis, patients who were younger, female, had comorbidities, and uninsured were significantly more likely to report care disruptions. On adjusted analysis, younger age and female sex remained significant predictors. In a sample-weighted subset of 1,600,587 patients (n=331), 291 (87.9%) reported virtual appointment use. There was no association with disruptions across breast, prostate, lung, and colorectal cancer groups. Conclusions: Approximately 1/3 of patients experienced disruptions to cancer care during the COVID-19 pandemic. Patients with younger age or female sex were more likely to have disruptions in care, which may reflect risk stratification strategies in the early stages of the pandemic. The longitudinal impact of these disruptions on outcomes merits further study. [Table: see text]