bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributions of screening, early-stage treatment, and metastatic treatment to breast cancer mortality reduction by molecular subtype in U.S. women, 2000-2017.
Authors: Caswell-Jin Jennifer Lee , Sun Liyang , Munoz Diego , Lu Ying , Li Yisheng , Huang Hui , Hampton John M. , Song Juhee , Jayasekera Jinani , Schechter Clyde , Alagoz Oguzhan , Stout Natasha K. , Trentham-Dietz Amy , Mandelblatt Jeanne S. , Berry Donald A. , Lee Sandra J. , Huang Xuelin , Kurian Allison W. , Plevritis Sylvia
Published: June 2022

1008

Background: Treatment for metastatic breast cancer has advanced since 2000, but we do not know if those advances have reduced mortality in the general population. Methods: Four Cancer Intervention and Surveillance Network (CISNET) models simulated US breast cancer mortality from 2000 to 2017 using national data on mammography use and performance, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, and competing mortality. Models compared overall and ER/HER2-specific breast cancer mortality rates from 2000 to 2017 relative to estimated rates with no screening or treatment, and attributed mortality reductions to screening, early-stage or metastatic treatment. Results of an exemplar model are shown. Results: The mortality reduction attributable to early-stage treatment increased from 35.8% in 2000 to 48.2% in 2017, while the proportion attributable to metastatic treatment decreased slightly from 23.9% to 20.6%. The increasing contribution of early-stage treatment reflects the transition of effective metastatic treatments to early-stage disease: accordingly, ten-year distant recurrence-free survival improved (82.5% in 2000, 87.3% in 2017; for ER+HER2+, 78.2% to 90.9%). Survival time after metastatic diagnosis also increased, doubling from 1.48 years in 2000 to 2.80 years in 2017, with the best survival for women with ER+HER2+ cancers (4.08 years) and worst for ER-HER2- (1.22 years). Conclusions: Advances in metastatic breast cancer treatment are reflected in lower population mortality, both through transition to early-stage treatment and gains for women with metastatic disease. These results may inform patient/physician discussions about breast cancer prognosis and expected benefits of treatment. [Table: see text]
Use of real-world data (RWD) to assess the utility of cell-free circulating tumor DNA (cfDNA) in identifying resistance to early treatment in advanced breast cancer (aBC).
Authors: Wander Seth Andrew , Weipert Caroline , Liao Jiemin , Zhang Nicole , Razavi Pedram
Published: June 2022

1011

Background: The approvals of CDK4/6 inhibitors (CDK4/6i) and alpelisib (a PI3Ka inhibitor, PI3Ki) have overhauled early treatment of hormone positive aBC. While some clinical trials have investigated mechanisms of resistance to these drugs, their impact on tumor evolution requires further exploration. Here we use cfDNA to examine molecular changes pre- and post-CDK4/6i or PI3Ki treatment and use RWD to assess the impact of putative resistance alterations on response to treatment. Methods: Patients (pts) with aBC were identified via the Guardant INFORM database and included if they had a cfDNA test within 90 days prior to therapy initiation and/or 90 days after therapy discontinuation with CDK4/6i or PI3Ki. Pts with RB1 loss of function (LOF) alterations (alts) who received CDK4/6i and pts with PTEN LOF alts who received PI3Ki were separately identified, and these cohorts were matched 1:3 with a RB1/PTEN negative population respectively, by age (+/- 5 years), sex, year of cfDNA test, and line of therapy. Log-rank tests were used to assess differences in time to discontinuation (TTD) and time to next treatment (TTNT). Results: Differences in the frequencies of certain alts detected in pts pre- and post-CDK4/6i or PI3Ki treatment are shown (Table). Pts with RB1 LOF alts prior to the start of CDK4/6i had significantly worse TTD and numerically worse TTNT versus controls (TTD = 3 mos vs 4.7 mos, p=0.018; TTNT = 7.3 mos vs 8 mos, p=0.082). Pts with PTEN LOF alts prior to start of PI3Ki had no significant difference in TTD or TTNT versus controls (TTD = 4.1 mos vs 4.1 mos, p=0.92; TTNT = 7.4 mos vs 7 mos, p=0.32). Notably, 54% of pts receiving CDK4/6i and 84% of pts receiving PI3Ki were on their third or later line of therapy. Conclusions: Using cfDNA, we were able to further characterize the resistance landscape of both CDK4/6i and PI3Ki, and identified specific ESR1, RB1 and PTEN alterations that appear likely to occur under the pressure of therapy. Our real-world analysis examining RB1 LOF alts added further evidence to suggest it may be both a primary and acquired resistance mechanism to CDK4/6i. As a non-invasive alternative to tissue biopsies, this data further illustrates that cfDNA can provide unique insight into tumor evolution and disease progression in the aBC setting. [Table: see text]
Characterization of alpelisib-associated hyperglycemia in metastatic breast cancer.
Authors: Shen Sherry , Chen Yuan , Carpio Andrea , Chang Cassandra , Iyengar Neil M.
Published: June 2022

1016

Background: For women with metastatic hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer, the combination of alpelisib and fulvestrant improves progression-free survival in those with PIK3CA mutations. Hyperglycemia is a major toxicity of PI3K inhibitors including alpelisib, which limits the clinical efficacy of these drugs due to interrupted/reduced dosing and discontinuation. In the SOLAR-1 trial that led to the Food and Drug Administration (FDA) approval of alpelisib, over 60% of patients developed hyperglycemia of any grade, and over 36% developed grade 3-4 hyperglycemia. Here we describe the incidence and treatment of alpelisib-associated hyperglycemia in a single center cohort. Methods: Patients with metastatic breast cancer who received alpelisib on a clinical trial or as part of standard care from 2013-2021 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Patient and tumor characteristics and pre-treatment body mass index (BMI), hemoglobin A1c, and serum glucose levels were abstracted from medical records. Alpelisib dose interruptions, reductions, or discontinuation was recorded as well as endocrinology consultation and use of anti-hyperglycemic agents. Date of progression and/or death were recorded where applicable. Results: 247 patients were included in this study, among whom 245 (99.1%) were female and 198 (80.1%) were white. 100 (40.5%) were treated on a clinical trial. Median baseline BMI was 25.4 kg/m2. Among 164 patients with baseline hemoglobin A1c levels available, 93 (56.7%) patients had normal hemoglobin A1c, 54 (32.9%) had prediabetes, and 17 (10.4%) had diabetes. 152 patients (61.5%) developed hyperglycemia of any grade; 56 (22.7%) developed grade 3 and 16 (6.5%) developed grade 4 hyperglycemia. The median time to onset of hyperglycemia was 16 days. BMI ≥25 kg/m2 or hemoglobin A1c ≥5.7% were strongly predictive of development of any-grade hyperglycemia ( p= 0.036 and p< 0.001, respectively) and grade 3-4 hyperglycemia ( p< 0.001 for both). Among those who developed hyperglycemia, 101 (40.9%) received treatment; 69 patients (27.9%) required only 1 anti-hyperglycemic agent whereas 9 (3.6%) required ≥3 anti-hyperglycemic agents. 49 (19.8%) were referred for endocrinology consult. In 66 patients (26.7%), alpelisib was held until resolution of hyperglycemia; 42 patients (17%) required dose reductions, and 11 (4.5%) discontinued alpelisib due to hyperglycemia. There was no significant difference in progression-free survival by hyperglycemia status or severity of hyperglycemia. Conclusions: Overweight BMI and hemoglobin A1c in the prediabetes or diabetes range were strongly predictive of developing alpelisib-associated hyperglycemia. Management of these co-morbidities prior to alpelisib treatment should be strongly considered.
Largest evaluation of acquired resistance to sotorasib in KRAS p.G12C-mutated non–small cell lung cancer (NSCLC) and colorectal cancer (CRC): Plasma biomarker analysis of CodeBreaK100.
Authors: Li Bob T. , Velcheti Vamsidhar , Price Timothy Jay , Hong David S. , Fakih Marwan , Kim Dong-Wan , Falchook Gerald Steven , Delord Jean-Pierre , Dy Grace K. , Ramalingam Suresh S. , Strickler John H , Kurata Takayasu , Wolf Juergen , Sacher Adrian G. , Addeo Alfredo , Prenen Hans , Hindoyan Antreas , Anderson Abraham , Ang Agnes , Skoulidis Ferdinandos
Published: June 2022

102

Background: Sotorasib, a specific, irreversible KRASG12C inhibitor, has been approved in multiple countries for adults with KRAS p.G12C-mutated locally advanced or metastatic NSCLC who received prior systemic therapy based on the global phase 1/2 CodeBreaK100 trial. Here we describe putative mechanisms of acquired resistance to sotorasib from the largest single dataset evaluated to-date. Methods: Patients with advanced KRAS p.G12C-mutated NSCLC or CRC from the CodeBreaK100 Ph1/2 trial who received sotorasib monotherapy at 960 mg once daily were analyzed for efficacy. Primary endpoint was objective response rate (ORR) assessed by central review. To investigate biomarkers of resistance to sotorasib, an exploratory endpoint was defined to examine acquired genomic alterations at disease progression. Plasma samples collected at baseline and progression were analyzed for genomic alterations with the 23-gene Resolution Bioscience ctDx Lung test for NSCLC and the 74-gene Guardant 360 ctDNA test for CRC. Acquired genomic alterations were defined by their absence at baseline and presence at progression. Results: In 174 pts with NSCLC and 91 pts with CRC-treated with sotorasib, the ORR were 41% and 12% respectively. Median progression-free survival and median overall survival were 6.3 months (mos) and 12.5 mos for NSCLC pts and 4.2 mos and 13.4 mos for CRC pts (median follow-up: 22.5 mos NSCLC; 12.5 mos CRC). A total of 67 NSCLC pts and 45 CRC pts had a plasma sample sequenced both at baseline and at progression. At least one new acquired genomic alteration at progression was detected in 19 (28%) NSCLC pts and in 33 (73%) CRC pts (Table). The acquired genomic alterations were heterogeneous in both NSCLC and CRC, with variants detected across multiple genes and pathways. The most prevalent putative pathway of resistance in both NSCLC and CRC was the receptor tyrosine kinase (RTK) pathway. Secondary RAS alterations occurred more frequently in CRC versus NSCLC pts (16% vs. 3%). Conclusions: Based on the largest descriptive dataset to-date, diverse mechanisms of acquired resistance occur in KRAS p.G12C-mutated NSCLC and CRC pts treated with sotorasib. New RTK pathway alterations frequently emerged at progression, highlighting the potential role for combining sotorasib with upstream inhibitors of RTK, such as SHP2 or EGFR inhibitors. Serial plasma DNA analysis revealed acquired resistance patterns that support the development of KRASG12C inhibitor combination therapies. Clinical trial information: NCT03600883. [Table: see text]
Chemotherapy shows better efficacy than endocrine therapy in patients with metastatic breast cancer with heterogeneous estrogen receptor expression.
Authors: Xie Yizhao , Du Xinyue , Tao Zhonghua , Zhao Yannan , Gong Chengcheng , Hu Xichun , Yang Zhongyi , Wang Biyun
Published: June 2022

1050

Background: Heterogeneity of estrogen receptor (ER) expression has long been challenges for diagnosis and treatment strategy of metastatic breast cancer (MBC). A novel convenient way of ER detection using 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) offers a chance to screen and analyze MBC patients with ER uncertainty. Methods: MBC patients who received 18F-FES PET/CT were screened and patients with both FES positive (FES+) and negative (FES-) lesions were enrolled in this study. Progression‐free survival (PFS) was estimated by Kaplan-Meier method and compared by log-rank test. Results: A total of 635 patients were screened and 75 of 635 (11.8%) patients showed ER uncertainty. 51 patients received further treatment and were enrolled in this study. Among them, 20 (39.2%) patients received chemotherapy (CT), 21 (41.2%) patients received endocrine-based therapy (ET) and 10 (19.6%) patients received combined therapy (CT+ET). CT showed better progression-free survival (PFS) compared to ET (mPFS 7.1 vs 4.6 months, HR 0.44, 95% CI 0.20-0.93, P = 0.03). CT+ET did not improve PFS compared to either CT or ET alone (mPFS 4.4 months, P > 0.2). Conclusions: 18F-FES PET/CT could identify patients with ER heterogeneity. Patients with ER uncertainty showed better sensitivity to CT rather than ET. Combined therapy of CT+ET did not improve treatment outcome.
Clinical implications of germline genetic testing stratified by ethnicity in a large colorectal cancer cohort.
Authors: Heald Brandie , Coughlin Sarah , Nielsen Sarah M. , Clark Dana , Hatchell Kathryn E. , Katona Bryson W , Esplin Edward D.
Published: June 2022

10504

Background: Germline genetic testing for patients (pts) with colorectal cancer (CRC) is currently recommended for those diagnosed prior to age 50, as well as other select cases based on personal and/or family history criteria. Whether universal germline multi-gene panel testing (MGPT) should be performed in all pts with CRC remains uncertain given the lack of large-scale studies examining MGPT in CRC across a diverse population. The present study aims to determine the yield, and potential clinical impact, of MGPT across a large CRC cohort. Methods: We conducted a de-identified retrospective cohort study of all pts with CRC who underwent MGPT (excluding patients who underwent testing limited to ≤10 genes) at a commercial laboratory between 03/2015-05/2021. We collected pts demographics from test requisition forms and results of germline MGPT. Clinically actionable PGVs were defined as variants in genes with reported CRC or polyposis risk, as well as other actionable genes associated with clinical management and/or therapeutic implications. Results: A total of 34,210 pts with a history of CRC underwent germline MGPT. These pts were primarily female (60.7%), White (70.6%), and 50 or older (68.8%), with 35.5% reporting an extra-colonic malignancy. Of this cohort, 4,577 (13.4%) were found to carry at least one PGV, with 2,925 (8.6%) having a PGV associated with increased risk of CRC or polyposis. Of all positive pts, 3,038 (66%) had PGVs with precision therapy or clinical trial implications while another 33% had PGVs with published management implications. Among pts under the age of 30 when tested, 23.3% had a clinically actionable PGV compared to 14.7% at age 30-39, 11.7% at 40-49, 12.9% at 50-59, 11.6% at 60-69, 8.9% 70-79, and 7.8% over the age of 80. When compared to pts identified as White, PGVs were more frequently identified in pts of Ashkenazi Jewish descent (p < 0.001) and less frequently identified in those who identified as Hispanic (p < 0.001). VUS was more frequently identified in pts identified as Black, Asian, or Hispanic (p < 0.001). Conclusions: This is the largest study to date examining MGPT in CRC, where we demonstrate high rates of clinically actionable variants across all age groups, self-reported racial/ethnic groups, and panel sizes, with 13% of all CRC pts having a PGV with precision therapy, clinical trial and/or published management implications.This is likely an underestimate as patients with strong clinical suspicion of hereditary CRC (Lynch, FAP) often receive a targeted panel of <10 genes and were excluded. The lower rate of PGVs in Hispanic pts and higher rate of VUS in Black, Asian and Hispanic pts underscores the historical underrepresentation of these pts and ongoing need to mitigate the associated healthcare disparities. Overall, this work supports consideration of broadening germline genetic testing criteria for patients with CRC.
Multicenter retrospective study of clinical genetic testing in patients with sarcoma.
Authors: Wilbur Helen Catherine , Cobain Erin Frances , Wiesner Georgia L. , Davis Elizabeth J. , Chugh Rashmi
Published: June 2022

10511

Background: Sarcomas are rare and diverse malignancies with a subset developing in the context of heritable cancer predisposition syndromes. Data surrounding the frequency of inheritance and patient/genomic findings are limited. We aimed to describe the characteristics of patients with sarcoma referred for clinical genetic testing and to determine the prevalence of pathogenic/likely pathogenic germline variants (PGV/LPGV). Methods: We performed retrospective chart reviews of patients with sarcoma referred to Michigan Medicine Cancer Genetics Clinic between 12/2006 and 1/2020 and Vanderbilt Hereditary Cancer Clinic between 1/2005 and 1/2019. Reviewers obtained medical/family history, cancer phenotype, and results of germline genetic testing. Descriptive analyses were performed to assess the prevalence of germline variants classified as pathogenic/likely pathogenic according to American College of Medical Genetics criteria. Associations with clinical factors were tested for using Fisher’s exact test or Wilcoxon rank-sum test. Results: One-hundred sixteen patients with sarcoma underwent genetic evaluation during a 15-year period. Mean age at time of visit was 46 years (SD, 17.6 years; range, 1-80 years). Sixty-nine patients (59%) were female. The most common reasons for referral were personal history of multiple malignancies (n = 69, 59.4%), first degree relative (FDR) with malignancy (n = 67, 57.7%) and young age at diagnosis (age ≤ 18, n = 18, 15.5%). Forty-eight patients (41.4%) had both a history of multiple malignancies and a FDR with a malignancy. Eight patients had a FDR with sarcoma (6.9%). Of the 110 patients who underwent germline testing, 53 patients (48.2%) had a PGV/LPGV. Identified germline variants and frequencies are listed in the Table. There was no statistical significance between young age at diagnosis, history of personal malignancies, FDR with sarcoma, FDR with one or more malignancies, or multiple FDRs with malignancy and presence of a PGV/LPGV. Conclusions: In this multicenter study, approximately half of patients with sarcoma referred for cancer genetic testing had a PGV/LPGV associated with hereditary predisposition to cancer. There was no identified positive predictive factor for germline variants. Though TP53 was the most common, over 20 genetic variants were identified, supporting the consideration of multigene panel testing. Our study is limited to patients who were both referred to and attended genetic evaluation. Yet, the high frequency of pathogenic germline variants observed highlights the necessity for further investigation of the prevalence of and predictive factors for germline mutations in all sarcoma patients. Identified germline variants. [Table: see text]
A multicenter study of clinical impact of variant of uncertain significance reclassification in breast, ovarian, and colorectal cancer susceptibility genes.
Authors: Makhnoon Sukh , Levin Brooke , Ensinger Megan , Mattie Kristin , Volk Robert Joseph , Zhao Zhongming , Mendoza Tito R. , Shete Sanjay , Samiian Laila , Grana Generosa , Grainger Andrew V. , Arun Banu , Shirts Brian , Peterson Susan K.
Published: June 2022

10512

Background: Up to 10% of all cancers are attributable to germline mutations and identifying mutation carriers is critical for cancer prevention. Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) with unknown impact on health, which can be clarified through reclassification. However, there is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, racial/ethnic differences, and the proportion of patients who undergo cancer preventive healthcare management as a result of VUS reclassification. Methods: Retrospective analysis of persons carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer genes who underwent genetic counseling at four geographically dispersed cancer care settings (in Texas, Florida, Ohio, and New Jersey) between 2013 and 2019, and followed until 2020. Results: Among 2,715 individuals, 3,261 VUS and 313 P/LP variants were reported and 11% (300/2,715) had a P/LP in addition to VUS. In total, 8.1% of all individuals with VUS experienced reclassifications, 87.1% of which were downgraded to benign or likely benign and 12.9% were upgraded to P/LP. Reclassification rates varied significantly among cancer care settings from 4.81% to 20.19% (overall p < 0.001). The reclassification pattern across genes suggests that VUS in most genes underwent reclassification at a rate proportional to their prevalence in the overall sample and occurred commonly in ATM, BRCA2, BRCA1, and CHEK2. Compared to their prevalence in the sample, reclassification rates were higher for Blacks (13.6% vs 19.0%), lower for Asians (6.3% vs 3.5%), and proportional for Whites and Hispanics. Median time to reclassification decreased steadily between 2014 and 2019 from 3.08 to 0.91 years. Overall, 11.3% of all reclassified VUS resulted in clinically actionable findings and 4.6% subsequently changed individuals’ clinical managements including prophylactic surgeries and intensive screenings for cancer prevention and early detection. Conclusions: In this large multisite study, VUS reclassification changed clinical management for 0.4% of all individuals. VUS reclassification may alter clinical management, has implications for precision cancer prevention, and highlights the need for standardized clinical practice guidelines and policies for returning reclassified results to patients.
Double jeopardy? A closer look at cancer histories of individuals with multiple germline pathogenic variants.
Authors: Horton Carolyn , Lo Min-Tzu , Yussuf Amal , Young Colin , Carraway Cassidy , Agaoglu Nihat Bugra , Bychkovsky Brittany L. , Rana Huma Q.
Published: June 2022

10514

Background: Germline multigene panel testing has led to the increased detection of multiple co-occurring pathogenic variants (PV) in the same individual. As this occurrence is still relatively rare, reports of these individuals have been limited. Therefore, we sought to describe the clinical features of individuals with multiple PV identified at a single high-volume diagnostic laboratory. Methods: We performed a retrospective review of demographics and clinical data for individuals with > 1 pathogenic or likely pathogenic variant (PV) who underwent hereditary cancer panel testing (5-67 genes) between May 2012 and April 2017. In recessive genes (i.e. MUTYH), PV were only included when biallelic. PVs with reduced penetrance ( APC p.I1307K; CHEK2 p.I157T, p.S428F, p.T476M) were excluded. In individuals with the most common combinations of genes, personal cancer history and age at cancer diagnosis was evaluated. Results: A total of 555 individuals were identified with multiple PVs. Most individuals were female (85.1%), had a personal history of cancer (73.3%) and 26.3% had two or more primary cancers. CHEK2 was most often seen in co-occurrence with a PV in a different gene (137 observations), followed by ATM (120 observations), BRCA2 (110 observations), and BRCA1 (88 observations). Among cases in which clinical information was provided (n = 545), the five most frequent co-occurring combinations were in ATM/CHEK2 (25), ATM/BRCA2 (23), BRCA1/CHEK2 (19), CHEK2/CHEK2 (16), and BRCA2/CHEK2 (14). Individuals with co-occurring PVs in CHEK2/CHEK2 had the youngest age at first cancer diagnosis (mean = 41.5y; median = 42y), the highest rate of breast cancer diagnoses and other cancer diagnoses (100.0% and 70.6% of individuals, respectively), and the highest proportion of individuals with > 1 primary cancer (52.9%). Conclusions: Our results indicate that individuals with two PVs in CHEK2 have an average age of cancer onset that is similar to individuals with either a BRCA1 or BRCA2 concurrent PV. Additionally, individuals with two PVs in CHEK2 were more likely to have multiple primary cancers as compared to others in the cohort with concurrent PVs including those with either a BRCA1 or BRCA2 concurrent PV (Table). Continued studies, including comparisons to individuals with one PV, will provide valuable insight to aid in counseling and management of individuals with multiple germline PV. [Table: see text]
Lung cancer risk prediction nomogram in Chinese female non-smokers.
Authors: Lan-Wei Guo
Published: June 2022

10530

Background: About 53% of lung cancers in females are not attributable to smoking worldwide. The aim was to develop and validate a simple and non-invasive model which could assess and stratify lung cancer risk in female non-smokers in China. Methods: A large-sample size, population-based study was conducted under the framework of a population-based Cancer Screening Program in Urban China (CanSPUC). Data on the lung cancer screening in Henan province, China, from October 2013 to October 2019 were used and randomly divided into the training and validation sets. Related risk factors were identified through multivariable Cox regression analysis, followed by establishment of risk prediction nomogram. Discrimination [area under the curve (AUC)] and calibration were further performed to assess the validation of risk prediction nomogram in the training set, and then validated by the validation set. Results: A total of 151,834 eligible subjects were included, with a mean age of 55.34 years. Subjects were randomly divided into the training (75,917) and validation (75,917) sets. Elder age, history of chronic respiratory disease, first-degree family history of lung cancer, menopause, and history of benign breast disease were the independent risk factors for lung cancer. Using these five variables, we plotted 1-year, 3-year, and 5-year lung cancer risk prediction nomogram. The AUC was 0.762, 0.718, and 0.703 for the 1-, 3- and 5-year lung cancer risk in the training set, respectively. In the validation set, the model showed a good predictive discrimination, with the AUC was 0.646, 0.658, and 0.650 for the 1-, 3- and 5-year lung cancer risk. Conclusions: We developed and validated a simple and non-invasive lung cancer risk model in female non-smokers. This model can be applied to identify and triage patients at high risk for developing lung cancers in female non-smokers.
Awareness of the link between HPV, cervical cancer, and HPV vaccination: An online survey among Polish women.
Authors: Kotowski Artur , Kotowska Maja Dominika , Zadroga Aleksandra , Hernas Katarzyna , Szymusik Iwona , Fal Andrzej Mariusz
Published: June 2022

10538

Background: In 2019 cervical cancer (CC) was the 7th most common malignant neoplasm in Polish women. Its incidence has been declining over the years, nonetheless the 5-year survival rate is still significantly lower than the EU average. Vaccination against human papillomavirus (HPV) is not included in the mandatory immunization schedule in Poland and is not reimbursed yet. The aim of the study was to assess women's awareness of the risk factors of CC (including the role of HPV) and the possibility of cancer prevention through HPV vaccination. Methods: The questionnaire prepared by the study team was aimed at women and conducted online using social network sites. The single/multiple-choice questions included knowledge about CC, HPV and HPV vaccination. Statistical analyses were performed using MS Excel 2016 and Medistica pvalue.io 2021 software in general population and age- dependent subgroups. Results: The total number of 3262 women participated in the study. The age subgroups were: aged ≤ 18 years (group 1): 1090 (33.4%), aged 19-25 years (group 2): 1615 (49.5%) and > 25 years (group 3): 557 (17.1%). Overall 81.4% of the respondents correctly associated HPV as the key factor of CC, 85.0% believed that CC could be prevented and 80.0% had heard of HPV vaccination before. In the last two parameters a statistically significant difference in age subgroups was observed (p < 0.001). Only 21.2% of the total number of respondents were vaccinated (26.2%, 22.0% and 9.2% in age groups 1, 2 and 3 respectively, p < 0.001). In all studied populations the following factors had the greatest influence on the decision to get vaccinated: parents’ advice – 54.8%, pediatrician recommendation – 15.7%, possibility of free vaccination offered by municipality – 11.6%, teachers’ advice - 9.7%, gynecologist recommendation - 8.2%. The main reasons behind not getting vaccinated were: high price (63.0%) and disbelief in efficacy (41.5%); only 12.2% respondents were afraid of possible side effects. 65.0% of the unvaccinated respondents declared willingness to get vaccinated in the future (71.5%, 66.1% and 52.0% in age groups 1, 2 and 3 respectively p < 0.001), 28.5% of the respondents were not confident of their decision at the time of submitting answers. Conclusions: As oncogenic types of human papillomavirus play a vital role in pathogenesis of CC, the HPV vaccination and cytological screening together with awareness-raising campaigns should be considered the best strategy for the prevention of CC, its early detection and increase in survival rates. Vaccine willingness remains at high level especially among young women, however the effectiveness of vaccination should be emphasized and the HPV free vaccination programs should be introduced by the state. The educational role of gynecologists needs to be enhanced.
Trends in the incidence of early-onset invasive colorectal cancer between 1990 and 2018, stratified by race/ethnicity, gender, and anatomic sub-sites among Pennsylvania residents.
Authors: Jackson Inimfon , Bley Edward , Goldberg Michael , Behme Matthew , Dourado Claudia M.
Published: June 2022

10543

Background: Recent data report a rising incidence of colorectal cancer in the younger population and epidemiological evidence is useful to enable clinicians understand evolving trends and better counsel patients on the potential risks/benefits of early screening. We explored the trends in incidence of early-onset invasive colorectal cancer by race/ethnicity, gender, and anatomic sub-sites. Methods: Repeated cross-sectional analyses were conducted among adults < 50 years diagnosed with invasive colorectal cancer between 1990-2018 in Pennsylvania using data from the Pennsylvania Department of Health Cancer Registry. Temporal trends in invasive cancer with age adjusted incidence rates according to race/ethnicity, gender, and anatomical sub-sites were assessed using the Enterprise Data Dissemination Informatics Exchange (EDDIE). Results: 16,154 cases of early-onset invasive colorectal cancer were diagnosed between 1990 and 2018. There was an increased incidence of invasive colorectal cancer in the general population especially when stratified by gender, race/ethnicity and among those < 40 years of age. While rates among Whites nearly doubled from 5.4 per 100,000 (95% Confidence Interval (CI): 4.9–6.0 per 100,000) population to 9.0 per 100,000 (95% CI: 8.2– 9.7 per 100,000) population, the rates in the Black population have been decreasing in recent years from a peak of 10.4 per 100,000 (95% CI: 8.4–12.7 per 100,000) population in 2011 to 7.3 per 100,000 (95% CI: 5.7–9.3 per 100,000) population in 2018. However, the Hispanic rates have remained stable. Across anatomical subsites, the rectum, rectosigmoid and sigmoid colon were found to have rising trends in incidence rates over time. Conclusions: There is increased awareness on the need for early diagnosis of colorectal cancer in the young Black population. However, we found trends toward increasing incidence rates among Whites while rates in the Black population are now decreasing. These findings accentuate the need for quality provider-patient communication during primary care visits with a goal to improve adherence to the new colorectal cancer screening guidelines regardless of race/ethnicity.
Interception versus prevention in cancer screening in a Medicare population: Results from the CRC-MAPS model.
Authors: Putcha Girish , Carroll Lauren N , Chandra Tarun , Piscitello Andrew
Published: June 2022

10546

Background: This study examines the impact of detecting cancer (interception) versus adenomas and cancer (prevention + interception) on clinical outcomes in a screen-naive Medicare cohort for a hypothetical colorectal cancer (CRC) screening test or a multicancer early detection (MCED) test that includes CRC. Methods: CRC-MAPS, a validated microsimulation model of the adenoma-carcinoma pathway that reproduced incidence reduction (IR) and mortality reduction (MR) consistent with CISNET models and a randomized controlled trial, was used to simulate perfect adherence to a hypothetical annual screening test among previously unscreened individuals free of diagnosed CRC. Four scenarios were examined: two cancer interception and two cancer prevention + interception. Individuals were screened from age 65 to 75. CRC IR and MR outcomes compared to no screening were aggregated from age 65 until death. Threshold analysis (#5) identified the ≥10mm adenoma sensitivity needed for a base-case cancer interception test (#1) to yield CRC MR equivalent to a near-perfect cancer interception test (#2). Results: The base-case interception scenario (#1) resulted in 5.6% CRC IR and 21.7% MR compared to 5.2% CRC IR and 25.9% MR for the near-perfect interception scenario (#2). The threshold analysis demonstrates that when the base-case interception scenario's ≥10mm adenoma sensitivity is increased from 1% to just 2.43% (#5), the resulting MR is equivalent to a near-perfect interception test. Accordingly, the cancer prevention + interception scenarios (#3, #4) resulted in CRC IR and MR outcomes 9.7-12.9x and 2.5-3.4x (respectively) as favorable as either cancer interception scenario due to adenoma detection. Conclusions: This analysis highlights that even small improvements in the detection of precancerous lesions for certain cancers (e.g., adenomas for CRC), which enable cancer prevention, can yield clinical benefits that meaningfully exceed those from tests that primarily detect cancer. Future studies will explore both benefits and burdens of different screening tests. Moreover, this approach will be applied to better understand the clinical utility of MCED tests. [Table: see text]
Clinical outcomes with alpelisib (ALP) plus fulvestrant (FUL) after prior treatment (tx) with FUL in patients (pts) with advanced breast cancer (ABC): A real-world (RW) analysis.
Authors: O'Shaughnessy Joyce , Woeckel Achim , Pistilli Barbara , Hegg Roberto , Vahdat Linda T. , Vuina Dragica , Asad ZVK Parisa(Fatemeh) , Smith Timothy W , Kim Julia , Krop Ian
Published: June 2022

1055

Background: ALP (α-selective PI3K inhibitor and degrader) + FUL was FDA approved and reflected in the NCCN guidelines in 2019 for pts with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2−) ABC with PIK3CA mutations following progression on or after endocrine-based therapy (ET). The Phase III SOLAR-1 trial excluded prior FUL, and data on ALP + FUL after FUL are limited. As cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + ET (including FUL) is the standard in the first line (1L) or second line (2L) for pts with HR+/HER2− ABC, more data on ALP + FUL post-FUL are needed. Here we report patterns and clinical outcomes on RW use of ALP + FUL in pts with HR+/HER2– ABC with prior FUL exposure. Methods: This retrospective study used de-identified electronic health record data from the ConcertAI Patient360 Breast Cancer data product sourced from US oncology centers. Adults with HR+/HER2− ABC treated with ALP + FUL (index tx) who received prior FUL (monotherapy or in combination) in the metastatic setting were included; pts with a PIK3CA negative test on or prior to the index were excluded. Pts were followed until date of death or last activity. RW progression-free survival (rwPFS), defined as first documented progression/death from ALP + FUL start date, was assessed. Results: This analysis included 157 pts (median age, 63 y [57-71 y]) who received ALP + FUL from 2019 to 2021, with 11.5% pts in 1L, 17.8% in 2L, 26.8% in third line (3L), and 43.9% in fourth line and beyond (4L+). Prior FUL tx included CDK4/6i + FUL (74.5%), FUL alone (33.8%), and non-CDK4/6i + FUL (21.0%). In pts who received ALP + FUL in 1L (n = 18), prior FUL exposure was in the same line without documented progression. In the metastatic setting, 28.0% of pts received > 1 FUL-containing regimen and/or 72.0% received prior chemotherapy (CT). At the median duration of follow-up (8.7 mo [4.1-12.5 mo]), the median rwPFS was 5.7 mo (4.0-7.3 mo) in the overall population. The median rwPFS was also analyzed by line of therapy (Table). In pts with CDK4/6i + FUL as immediate prior therapy (n = 39), the median rwPFS was 6.2 mo (3.0-9.1 mo); 79.5% of these pts received ALP in ≤ 3L. At the time of analysis, 107 pts (68.2%) had discontinued ALP + FUL; the median time to discontinuation was 4.7 mo (3.7-6.1 mo). Following discontinuation of ALP + FUL, CT was the most common subsequent therapy (33.8%). Conclusions: This analysis on RW data from early years of ALP access in the US shows clinical benefit of ALP + FUL in pts with HR+/HER2− ABC with PIK3CA mutation even when exposed to prior FUL, confirming the oncogenic dependence of the tumor on the PIK3CA mutation. [Table: see text]
LVEF decline in relation to body composition among women treated for breast cancer: WF-97415.
Authors: Reding Kerryn , O'Connell Nathaniel S. , Cheng Richard , Nguyen Johnny , Ladd Amy , Jordan Jennifer , Ky Bonnie , Vasbinder Alexi , Zaha Vlad , Lucas Alexander , Calhoun Tonya , Hackney Mary Helen , Bellissimo Moriah , D'Agostino Ralph , Lesser Glenn Jay , Hundley W. Gregory
Published: June 2022

10556

Background: Despite an improvement in survival from breast cancer (BC), many women experience cardiotoxicity. Left ventricular ejection fraction (LVEF) is reduced by an average of 9.7% in women receiving anthracyclines. Obesity and central adiposity at BC diagnosis may influence risk of LVEF decline. We sought to examine associations between body composition and LVEF decline in the UPBEAT (Understanding and Predicting Fatigue, Cardiovascular Decline, and Events After Breast Cancer: WF-97415) study, which was conducted in collaboration with NCI Community Oncology Research Program. Methods: The analytic cohort was comprised of 167 women treated for stage I-III BC with chemotherapy and/or radiation in the UPBEAT prospective study, in whom LVEF was obtained at baseline (pre-treatment) and 3 months. Linear regression was used to examine LVEF decline in relation to 1) waist circumference (WC) and body mass index (BMI) at baseline and 2) changes in WC and BMI during BC treatment. All models were adjusted for age and race. Results: In this cohort (mean [SD] age: 55.7 [10.8] yrs; in whom 75% were white; 19% were Black), the mean (SD) LVEF at baseline was 60.7 (6.7)% with a mean decline of 2.7 (7.2)% from baseline to 3-months. Both WC and BMI at BC diagnosis were associated with LVEF decline during follow-up (Table). For each additional inch in WC, EF decreased by 0.25% points at 3 months (P=0.024); for each additional kg/m2 in BMI, EF decreased by 0.2% points at 3 months (P=0.007). Reduced BMI during treatment was associated with LVEF decline, whereas a change in WC was not. Each kg/m2 reduction in BMI was associated with a 0.4% point decrease in LVEF (p=0.037). Anthracycline use was associated with a 1.89% point decline in LVEF at 3 months versus non-users (p=0.049). After additional adjustment for anthracycline use, baseline WC remained statistically significantly associated with LVEF decline to the same degree. Conclusions: These data show that central adiposity at BC diagnosis is associated with LVEF decline during treatment, even after controlling for anthracyclines. Loss of central adiposity was not associated with LVEF decline, whereas BMI loss during treatment was. This suggests that shifts in body composition during BC treatment, potentially via loss of muscle mass, are important to monitor in patients. Future work should examine how changes in body composition, particularly changes in skeletal muscle and adipose tissue depots, influence cardiac dysfunction in BC patients during treatment. Funding: 2UG1CA189824, R01CA199167, 2UG1CA189828. [Table: see text]
Analysis of genomic alterations in pan-cancer from a large real-world Chinese population.
Authors: Dong Zhouhuan , Gao Jie , Zhu Fengwei , Gai Fei , Su Wenqing , Liang Zhixin , Tian Xiaodong , Shi Huaiyin
Published: June 2022

10568

Background: Effective targeted therapy sorely depends on comprehensive and precise genomic profiling. Besides, single nucleotide variations (SNVs) and InDels, gene fusions, as drivers and therapeutic targets of great importance, are not yet well characterized in Chinese patients. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues from 1,384 pan-cancer patients were collected and sequenced using next-generation sequencing (NGS) targeting 40 cancer genes including SNV, fusion and assessing copy number variation (CNV) (AmoyDx HANDLE Classic Panel). qPCR and fluorescence in situ hybridization (FISH) were further applied to verify NGS detected fusion genes. Results: 1,384 patients were recruited including 890 lung cancers, 272 colorectal cancers, 174 gastric cancers, and 48 endometrial cancers. The prevalence of fusion genes (5.49%), including ALK-fusion (2.67%), ROS1-fusion (0.94%), RET-fusion (0.72%), NRG1-fusion (0.29%), and NTRK-fusion (0.07%), was nearly double the frequency of previously reported data from East Asians. Prevalence of fusion genes varied in different types of cancers. For instance, ALK (3.7%), ROS1 (1.5%), RET (1.0%) and NRG1 (0.2%) fusions were largely found in patients with non-small cell lung cancer (NSCLC), and were rarely detected in other cancer types. Further analysis of genomic alterations in fusion-positive patients revealed that, TP53 (21%) was the most frequently co-occurred mutated gene with ALK fusion, while RET fusions and ROS1 fusions were rarely accompanied by other mutated genes. In addition, two patients with RBPMS- NRG1 fusion were accompanied by BRAF and RB1 mutations, whereas no co-occurred mutation was found in patients with other partners of NRG1. Patients with inconsistent results of RNA-based NGS and FISH validation fusions are still being followed for treatment and survival, updated data will be available at the time of the presentation. Conclusions: Genomic alterations in real-world Chinese populations have specific characteristics, especially fusion genes. Further characterization of these variants is essential for clinics to guide appropriate targeted therapies.
Characteristics of patients with neuroendocrine tumors in the United States: A study of 392,412 patients.
Authors: Reddy Ravali A. , Liao Cheng-I , Johnson Caitlin Ruth , Tian Chunqiao , Darcy Kathleen M. , Kapp Daniel Stuart , Chan John K
Published: June 2022

10572

Background: To evaluate the characteristics and trends amongst patients with neuroendocrine tumors in the United States. Methods: Data was obtained from the United States Cancer Statistics database from 2001 to 2018. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate characteristics and trends of these cancers per 100,000. The age-adjusted incidences were determined based on the standard population in the United States from 2000. Results: Of 392,412 patients with neuroendocrine tumors, 53.1% were identified in women and 46.9% in men. White, Black, Hispanic, Asian/Pacific Islander and unknown race comprised 73.6%, 14.1%, 7.8%, 2.7%, and 1.7% of the patient population respectively. The majority (64.7%) of tumors originated from the digestive system, followed by 24.5% from the respiratory system. In 2018, the incidence of all neuroendocrine tumors was higher in older (70-79 years) patients as compared to younger (< 50 years) ones at 30.17 vs. 2.79/100,000, in women as compared to men at 8.36 vs. 7.77/100,000, and in White patients as compared to Black, Hispanic, and Asian/Pacific Islander patients (10.82, 10.15, 5.08 and 4.80/100,000 respectively). Amongst different types of neuroendocrine tumors, those originating from the digestive system had the highest incidence at 6.72/100,000 in the year 2018 with colon tumors being the most common subtype. On trend analysis, the groups with the highest annual percent increase included: younger (< 50 years) patients increasing at 5.06%, Hispanic patients rising at 6.44%, and appendiceal tumors increasing at 12.89% per year. On intersection analysis, Black patients between the ages of 70-79 had the highest incidence at 33.39/100,000, while younger (< 50 years) Hispanic patients had the largest increase at 6.22% per year. Conclusions: The incidence of neuroendocrine tumors has increased over our study period. The highest incidence was found in older Non-Hispanic Black patients, with younger Hispanic patients having the highest annual percent increase. Further studies are warranted to better characterize the reasons for these trends and disparities amongst minority patients affected by these tumors.
Genetic counselling and testing for breast and ovarian cancer in Asia: A multinational survey of unmet needs.
Authors: Kwong Ava , Tan David Shao Peng , Ryu Jai Min
Published: June 2022

10586

Background: Enabling equitable access to healthcare services among women remains a challenge in Asia. Differences in the presentation and treatment stage contribute to disparities in cancer outcomes. Genetic testing provides accurate risk assessment to help guide personalised preventative and treatment options. However, there is a critical need for research to further our understanding of barriers in leveraging optimal benefits of genetic testing and counselling (GT&C) to address cancer among women. Methods: A team of multinational experts was assembled to form the Asian Consensus and Recommendations on Genetic Testing and Counselling (ACROSS) Consortium to assess the challenges in adoption of GT&C for patients with breast and ovarian cancer in Asia. Critical publications were identified, and a pre-meeting questionnaire was developed. The questionnaire was refined to align with the objectives over iterations, and final approval was obtained from the steering committee. Survey responses were gathered from oncologists from ten countries across Asia. The expert committee discussed the survey results to highlight (1) current knowledge, attitude, and practices; (2) unmet needs and gaps; and (3) recommendations for addressing critical obstacles. Results: Adoption of GT&C for cancer is low in Asia. Lack of time, resources, and access to genetic counsellors are major difficulties faced. In most cases, the practising oncologists provide pre-test genetic counselling and communicate test results. For breast cancer (BC), most experts preferred germline testing only, with few opting for somatic testing if germline testing was negative. The agreement was lower among the ovarian cancer (OC) experts, with advocates for either germline or somatic testing or both. There was a lack of consensus on clinical criteria for selecting suitable candidates for genetic testing and the use of multiple gene panel germline testing. The need for government-aided subsidies and training programmes was highlighted. Conclusions: Recommendations from the expert panel included (1) development of guidelines and criteria to identify candidates suitable for GT&C; (2) training healthcare professionals with required competencies; (3) improving accessibility and affordability; (4) increased patient education and awareness; and (5) adoption of GT&C into the national healthcare system. The consortium agreed that a multifaceted plan of action combining the expertise of clinicians, scientists, and policymakers is required to facilitate uptake of GT&C in Asia. [Table: see text]