US National Cancer Research Articles

Evaluation of Overall Survival and Barriers to Surgery for Breast Cancer Patients Treated Without Surgery

Surgery remains the foundation of curative therapy for non-metastatic breast cancer, but a substantial proportion of patients do not undergo surgery. Evidence is limited regarding overall survival (OS) outcomes and factors associated with lack of surgery. We sought to measure OS among patients with breast cancer who do not undergo surgery, and assess factors for association with lack of surgery and OS.Retrospective cohort study of patients in the US National Cancer Data Base from 2004-2016. The dataset comprised 2,696,734 patients; excluding patients with unknown surgical status or stage IV, cT0, cTx, or pIS, metastatic or recurrent disease resulted in 1,192,294 patients for analysis. Descriptive statistics were used to summarize patient characteristics. Chi-square tests and Wilcoxon rank-sum were used to test for differences between variables between groups. OS was analyzed utilizing the Kaplan-Meier method for non-surgical patients diagnosed in 2010-2015 to account for receptor status (Median follow-up time 34 months). The Cox proportional hazards model was used to assess association of risk factors with OS.Of the 1,192,294 patients, 50,626 (4.3%) did not undergo surgery. Socioeconomic factors that were more prevalent in the non-surgical cohort were Black race, age > 50 years, lower income, uninsured or public insurance, and lower education; this group was also more likely to have more comorbidities, higher disease stage, and more aggressive disease biology. Only 3,689 non-surgical patients (7.3%) received radiation therapy (RT). Median OS time for all patients who did not have surgery was 58 months (3-year and 5-year OS rates 63% and 49%). Median OS times were longer for patients who received chemotherapy (80 vs 50 months) and RT (85 vs 56 months). On multivariate analysis, age, race, income, insurance status, comorbidity score, disease stage, tumor subtype treatment facility type and location, and receipt of RT were associated with OS. On subgroup analysis, receipt of chemotherapy improved OS for patients with high-risk (triple-negative, HER2+) disease, whereas receipt of RT led to improved OS for patients with ER+ and favorable (ER+, early-stage, age > 60) disease.More than 4% of women with non-metastatic breast cancer do not undergo surgery for their cancer, particularly those with more aggressive disease, of minority race/ethnicity and lower socioeconomic status. Despite its known benefits, RT was significantly underused. This study provides one of the first benchmarks of survival outcomes for patients who do not undergo surgery for breast cancer, and highlights a potential role for increased use of RT. Additionally this report highlights significant disparities effecting women of minority race/ethnicity and lower socioeconomic status.

Toxicity Index, Patient-Reported Outcomes, and Early Discontinuation of Endocrine Therapy for Breast Cancer Risk Reduction in NRG Oncology/NSABP B-35.

The US National Cancer Institute Moonshot initiative calls for improving analysis and reporting of toxicity to inform treatment tolerability. We used existing clinician-reported adverse event (AE) and patient-reported outcome (PRO) questionnaire data from the randomized, double-blind NSABP B-35 clinical trial to explore reasons for anastrozole and tamoxifen discontinuation. Postmenopausal women with ductal carcinoma in situ treated with breast-conserving therapy were randomly assigned to anastrozole or tamoxifen for 5 years. The primary outcome for this analysis was time to treatment discontinuation. AEs were collected every 6 months post-random assignment from all 3,104 participants and summarized using the Toxicity Index (TI). PRO data were collected at baseline and every 6 months from 1,194 participants. Univariate and multivariable analyses of time to treatment discontinuation were performed using Cox regression models with TIs and PROs as time-dependent covariates. Of 3,046 analyzed participants, 869 (28.5%) discontinued treatment prematurely. In multivariable analysis, when both baseline PROs and on-treatment AEs were considered, thrombosis and arthralgia AEs were associated with discontinuation of both tamoxifen and anastrozole; additional AEs associated with discontinuation varied by drug. In addition, baseline pain interference, hot flashes, and unhappiness were associated with tamoxifen discontinuation (n = 589; overall Harrell's C-statistic 0.686 [95% CI, 0.640 to 0.732]); no baseline PROs were associated with anastrozole discontinuation (n = 589; overall Harrell's C-statistic 0.656 [95% CI, 0.630 to 0.681]). When only baseline PROs were examined, pain interference, hot flashes, and unhappiness were associated with shorter time to discontinuation of tamoxifen; only hot flashes were associated with discontinuation of anastrozole. Analysis of AEs using the TI yielded important insights into reasons for discontinuation of endocrine therapy that was enhanced by the addition of PRO baseline and treatment-emergent symptoms.

P04.08 Biopsy-only glioblastoma (BO-GBM) as a heterogeneous group of patients

Abstract BACKGROUND “Biopsy-only” glioblastoma is associated with a heterogeneous functional and survival outcome. BO-GBM patients is an understudied group of patients associated to a poor outcome, which has been reported to represent 21% of histologically confirmed GBM in the US National Cancer Data Base. Pattern of care included radiotherapy-temozolomide (RT-TMZ) standard regimen completed in 15% of patients, any other form of oncologic treatment in 60%, and supportive care alone in 25% of patients. Our objective was to explore pattern of care and prognosis associated to BO-GBM in our center. MATERIAL AND METHODS Patients with BO-GBM included in a prospective regional glioma SIRIC cohort initiated in 2014 and closed in 2017 were retrospectively reviewed for patients characteristics, MRI finding, treatment allocation and delivery. PFS and OS were analyzed. RESULTS Of 535 patients included in the cohort, 86 patients were referred > 3 months post-surgery and were excluded from this analysis while 449 patients were included at initial surgery, of which 158 patients (35%) underwent biopsy only. Of 158 patients, 18 patients were excluded for missing data leaving 139 patients for the present analysis. Fifty-four (39%) were referred to RT-TMZ (50 patients completed concomitant treatment), 68 (49%) considered unfitted for RT received chemotherapy upfront (CT-UF) (of which 4 were subsequently referred to RT), 17 (12%) were referred to palliative care only (PC). Groups differed at baseline for age (mean 60, 68, and 69 years, for RT-TMZ, CT-UF, and PC respectively); for KPS (70, 60, and 50 for RT-TMZ, CT-UF, and PC respectively); for mean tumor surface measured on gadolinium-enhanced T1-weighted (793, 1420, 1412 mm2 for RT-TMZ, CT-UF, PC); for tumor extension (bilateral in 6.4% and 29.3% for RT-TMZ and CT-UF respectively); for mean steroid intake (45, 60, 100 mg daily respectively). Median OS was 14 months (95% CI, 9.65–18.71), 8 months (95% CI, 4.62–7.67), and 2 months (95% CI, 0.67–3.33) for RT-TMZ, CT-UF, and PC respectively. CONCLUSION Inoperable GBM constitute a large and heterogeneous population in which one third of patients are amenable to standard of care, with survival outcome close to the one of patients who underwent surgery. Patients considered unfit for RT-TMZ at diagnosis fail to be referred subsequently to RT after CT and exhibit a poor survival outcome. Thus, reliable criteria are needed to help selecting patients for adequate treatment while new strategies are warranted for BO-GBM unfit for RT.

Evidence of intergenerational transmission of diethylstilbestrol health effects: hindsight and insight.

This review summarizes key findings from the US National Cancer Institute (NCI) diethylstilbestrol (DES) Combined Cohort Study with a focus on the results of the NCI Third Generation Study, a cohort of DES-exposed and -unexposed granddaughters. Findings to date from the Third Generation Study are discussed in the context of other research efforts and case reports, suggesting an intergenerational heritability of DES-related effects. The DES story serves as a model for the influence of endocrine disrupting chemicals on human health. It also serves as a warning of the special hazards of pregnancy exposures, and more broadly, of the potential for invisible health consequences arising from new or changing exposures.

Adolescent and young adult enrollment to a National Cancer Institute-sponsored National Clinical Trials Network Research Group over 25 years.

Adolescent and young adult (AYA) patients with cancer have not seen the same improvements in survival as younger (pediatric) patients and older patients (adults 40 years old or older). This may be related to their lower participation in clinical trials. This study examined AYA patient accrual to SWOG Cancer Research Network phase 1 to 3 clinical treatment trials for 29 cancers over 25 years (January 1996 to December 2020). Trial enrollments for AYA patients (15-39 years old) were compared with trial enrollments for older patients (40 years old or older) in SWOG and with US AYA cancer population rates derived from US Census and National Cancer Institute/Surveillance, Epidemiology, and End Results data. In total, 84,219 patients were enrolled in SWOG treatment trials, including 7109 AYA patients (8.4%); in contrast, AYAs constituted 3.8% of the US cancer population. By histology, the highest proportions of AYA patients were in trials for Hodgkin disease (825 of 1220; 67.6%) and acute lymphocytic leukemia (350 of 678; 51.6%), whereas breast cancer trials had the greatest number of AYA patients (3032 of 32,693; 9.3%). SWOG AYA patients were more often female (68.8% vs 58.7%; P < .001), Black (10.1% vs 8.2%; P < .001), and Hispanic (10.6% vs 5.6%; P < .001) than SWOG patients who were 40 years old or older, and they were more often female (68.8% vs 65.1%; P < .001) but less often Black (10.1% vs 11.8%; P < .001) or Hispanic (10.6% vs 12.8%; P < .001) than AYA patients in the US cancer population. AYA patients with cancer were well represented in SWOG clinical trials in comparison with US cancer population patients with the same cancers. The SWOG AYA population was more racially/ethnically diverse than older SWOG patients, although it was less diverse than the US AYA cancer population. Adolescent and young adult (AYA) patients with cancer (aged 15-39 years) have not seen the same improvements in survival as younger (pediatric) patients and older patients (adults 40 years old or older). This may be related to their lower participation in clinical trials. This study evaluated the extent to which AYA patients were enrolled in a large, National Cancer Institute-sponsored network group over 25 years (1996-2020). Overall, 8.4% of the enrolled patients (7109 of 84,219) were AYAs; this was twice the corresponding rate of 3.8% in the US cancer population. AYA patients were also more racially/ethnically diverse than older trial patients, although they were less racially/ethnically diverse than the US AYA cancer population.

Impact of racial disparities on potential years of life lost due to gynecologic cancer in the United States: trends from 1975 to 2017 based on SEER database

<h3>Objectives:</h3> Gynecologic cancer is a major health problem in the United States. We assessed potential years of life lost (PYLL) in women secondary to gynecologic cancer in the United States from 1975 to 2017 using the SEER (Surveillance, Epidemiology and End Results) database. We also report race-adjusted trends in PYLL to highlight racial disparities impacting mortality in gynecologic malignancies. <h3>Methods:</h3> We extracted data from the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 2019 dataset using ICD-O codes for cervix, corpus and uterus, ovary, vulvar, vaginal and other gynecologic cancers. Patients who were diagnosed between 1975-2017 were included. Survival time was estimated by using recorded age of diagnosis and survival data from SEER. Potential years of life lost up to and including age 75 years were calculated after stratifying for tumor site. Statistical analysis was done using One-Way ANOVA test. <h3>Results:</h3> A total of 342159 patients were included in the analysis. Total 1825109 potential years of life were lost due to gynecologic cancers from 1975 to 2017. Uterine followed by ovarian were the two most common gynecologic malignancies with highest number of recorded cases (46.4% and 24.8% respectively). Median PYLL for cervical cancer (12.7 years) was higher than other gynecologic malignancies likely due to early median age of diagnosis (49 years). Across the board, for every subtype of gynecologic malignancy reported, median PYLL for Non-Hispanic White (NHW) population was lower as compared to women from all other racial and ethnic groups. p-value was significiant for every tumor type (Table 1). For NHW females with uterine cancer median PYLL was -0.8 years suggesting likelihood of survival past age of 75 years. <h3>Conclusions:</h3> Analysis of real-world data represents a clear trend pointing towards racial and ethnic disparities in PYLL due to gynecologic malignancies in the United States. Health care policies and efforts need to be focused on improving access to treatment and affordability of medical care for population groups at higher risk of losing quality life years.

Incidence of suicide mortality among childhood cancer survivors: A population-based retrospective study

The aim of our study was to investigate the suicide rates among childhood cancer survivors and assess factors associated with higher suicide risk. A review of data from Surveillance, Epidemiology, and End Results (SEER) program from 1975 to 2016 was performed for this study. This program is based on the US population and is supported by the US National Cancer Institute (NCI). Survivors diagnosed with childhood cancer were recorded. There were 40 suicides among 567,233 person-years, giving a suicide rate of 7.1 per 100,000 person-years. Compared with cancer diagnosed between 10 and 14 years old, survivors with cancer diagnosed between 0 and 4 years old had lower suicide risk. Females had a lower risk of suicide than males. Compared with survivors of thyroid cancer, the aHRs were 0.16 for acute lymphocytic leukemia, 0.15 for nodal Hodgkin's lymphoma, 0.14 for brain cancers and 0.09 for kidney cancers. Most suicides occurred after 15 years old. Suicide was a problem for survivors, especially those with thyroid cancer. Beside treating patients holistically, early psychological interventions such as communicating effectively, providing social support and follow-up care related to psychological health are needed.

Evaluation of overall survival and barriers to surgery for patients with breast cancer treated without surgery: a National Cancer Database analysis

Surgery remains the foundation of curative therapy for non-metastatic breast cancer, but many patients do not undergo surgery. Evidence is limited regarding this population. We sought to assess factors associated with lack of surgery and overall survival (OS) in patients not receiving breast cancer surgery. Retrospective cohort study of patients in the US National Cancer Database treated in 2004–2016. The dataset comprised 2,696,734 patients; excluding patients with unknown surgical status or stage IV, cT0, cTx, or pIS, metastatic or recurrent disease resulted in 1,192,294 patients for analysis. Chi-square and Wilcoxon rank-sum tests were used to assess differences between groups. OS was analyzed using the Kaplan–Meier method with a Cox proportional hazards model performed to assess associated factors. In total 50,626 (4.3%) did not undergo surgery. Black race, age >50 years, lower income, uninsured or public insurance, and lower education were more prevalent in the non-surgical cohort; this group was also more likely to have more comorbidities, higher disease stage, and more aggressive disease biology. Only 3,689 non-surgical patients (7.3%) received radiation therapy (RT). Median OS time for the non-surgical patients was 58 months (3-year and 5-year OS rates 63% and 49%). Median OS times were longer for patients who received chemotherapy (80 vs 50 (no-chemo) months) and RT (85 vs 56 (no-RT) months). On multivariate analysis, age, race, income, insurance status, comorbidity score, disease stage, tumor subtype, treatment facility type and location, and receipt of RT were associated with OS. On subgroup analysis, receipt of chemotherapy improved OS for patients with triple negative (HR 0.66, 95% CI 0.59–0.75, P < 0.001) and HER2+ (HR 0.74, 95% CI 0.65–0.84, P < 0.001) subgroups while RT improved OS for ER+ (HR 0.72, 95% CI 0.64–0.82, P < 0.001) and favorable-disease (ER+, early-stage, age >60) (HR 0.61, 95% CI 0.45–0.83, P = 0.002) subgroups. Approximately 4% of women with breast cancer do not undergo surgery, particularly those with more aggressive disease and lower socioeconomic status. Despite its benefits, RT was underutilized. This study provides a benchmark of survival outcomes for patients who do not undergo surgery and highlights a potential role for use of RT.

Abstract 20: Development of International Cancer Research Partnerships Through the NCI US-Latin American-Caribbean HIV/HPV-Cancer Prevention Clinical Trials Network (ULACNet)

Abstract Purpose: Persons living with HIV have elevated risks of HPV-related cervical, anogenital, and oropharyngeal cancers. Yet, research on optimization and implementation of prevention interventions (prophylactic HPV vaccination, cervical and anogenital cancer screening and triage, and precancer therapeutics) for HPV-related cancers among persons living with HIV has been limited. With a goal to expand this evidence, and building on strong academic research partnerships developed for HIV research between institutions in the US and the Latin American and the Caribbean (LAC) region, the US National Cancer Institute (NCI) initiated ULACNet, a new Cooperative Agreement clinical trials network in 2019. Methods: ULACNet comprises of three Partnership Centers each led by US-based institutions (University of California San Francisco, Weill Medical College of Cornell University, and Fred Hutchinson Cancer Research Center), working collaboratively with US and LAC institutions and with the NCI to develop and conduct multicenter prevention clinical trials focused on filling key scientific gaps and evaluating novel interventions. Results: ULACNet encompasses six countries (US, Mexico, Puerto Rico, Brazil, Peru, and Dominican Republic), twenty partner institutions, and over 100 collaborating scientific investigators, clinical and public health practitioners, research staff, and patient advocates. ULACNet will collaboratively conduct nine prevention clinical trials (two prophylactic HPV vaccine trials in adults and perinatally-HIV infected adolescents, three trials for clinical validation of molecular biomarkers and imaging technologies for screening and triage, two candidate HPV therapeutic vaccine trials, and two trials of topical therapeutic agents). Facilitation across network partners is achieved via a Coordinating Committee and three Working Groups (focused on HPV testing and screening, precancer treatment, and recruitment and retention activities). Conclusion: ULACNet seeks to leverage established academic global health partnerships to conduct high quality collaborative clinical trials to inform clinical practice and ultimately reduce the burden of highly preventable HPV-related cancers in persons living with HIV worldwide. Citation Format: Emma Brofsky, Margaret House, Brandy Heckman-Stoddard, Mostafa Nokta, Satish Gopal, Vikrant Sahasrabuddhe. Development of International Cancer Research Partnerships Through the NCI US-Latin American-Caribbean HIV/HPV-Cancer Prevention Clinical Trials Network (ULACNet) [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 20.

Abstract 53: Promoting WHO's Cervical Cancer Elimination Goals ‘90-70-90' by Developing, Implementing, and Evaluating the ECHO Latin America (ECHO ELA) Program

Abstract Purpose: Cervical cancer is one of the leading causes of cancer deaths among women in some countries in the Region of the Americas.1 Cervical cancer is preventable through HPV vaccination, screening and treatment of precancerous lesions, and can be effectively treated if diagnosed early.2 Methods: Under the framework of the Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem, the US National Cancer Institute (NCI), the University of Texas MD Anderson Cancer Center (MD Anderson) and the Pan American Health Organization/World Health Organization (PAHO/WHO) partnered to develop ECHO Latin America (ECHO ELA). ECHO ELA is modeled on Project ECHO® (Extension of Community Healthcare Outcomes) a hub-and-spoke knowledge-sharing approach where expert teams lead virtual didactic lectures and case discussions, amplifying the capacity for participants to deliver best practice programs to their regions. ECHO ELA consists of monthly, Spanish-language telementoring conferences about cervical cancer prevention and control. The program targets Ministries of Health, Immunization Program Managers and key cervical cancer stakeholders in Latin American (LA) countries. Its primary goal is to assist countries in reaching their WHO cervical cancer elimination goals “90-70-90:” vaccinating 90 percent of girls against HPV by the age of 15, screening 70 percent of women for cervical cancer at ages 35 and 45, and treating 90 percent of women diagnosed with pre-invasive cervical lesions or cervical cancer. Results: To date, 222 participants from 21 countries have registered. Seven sessions have been held averaging 93 participants per session. 85 participants completed the baseline survey addressing priorities, capacity, and desired outcomes. Baseline, mid-year evaluation results, within the COVID-19 context, and learned lessons will be presented. Conclusion: ECHO ELA is potentially an effective tool to convene participants from multiple countries to enhance collaboration and support countries' progress towards the elimination of cervical cancer in the Americas. Citation Format: Sandra L. San Miguel-Majors, Edward L. Trimble, Doug Lowy, Melissa Lopez-Varon, Ellen Baker, Kathleen Schmeler, Silvina Arrossi, Maria Tereza da Costa Oliveira, Mauricio Maza, Jane R. Montealegre, Mila P. Salcedo, Lucia Helena de Oliveira, Silvana Luciani. Promoting WHO's Cervical Cancer Elimination Goals ‘90-70-90' by Developing, Implementing, and Evaluating the ECHO Latin America (ECHO ELA) Program [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 53.

Abstract LB084: High cardiovascular disease mortality after central nervous system tumor diagnosis: Evidence from UK and USA population-based study

Abstract Background Accumulating data show cardiovascular disease (CVD) is a major cause of death in many cancer patients supporting cardio-oncology epidemiology and clinical studies. Although rare, patients diagnosed with brain and central nervous system (CNS) tumours have significant morbidity and mortality. Whether CVD is a major cause of death and if this differs by malignancy has not been comprehensively assessed. Methods We aimed to examine the risk of CVD mortality in patients diagnosed with malignant and non-malignant CNS tumours using cancer registry data in the UK and US. Analyses were conducted using Wales Cancer Registry, UK (Secure Anonymised Information Linkage, SAIL) for 8,743 patients diagnosed from 2000-2015 (54.9% of which died); and the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) for 188,526 patients diagnosed from 2005-2015 (40.0% of which died). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated for CVD cause of death (heart disease, cerebrovascular disease, hypertension, atherosclerosis, and aortic aneurysm/dissection) and adjusted for age, sex and calendar year compared to all Welsh and US residents. SMRs were stratified by tumour types (malignant and non-malignant tumours) and main histologic types (glioma and meningioma). Results CVD is the second major cause of death for CNS tumour patients in SAIL and SEER (9.5% &amp; 12.1%, respectively). Patients with malignant and non-malignant CNS tumours had excess CVD mortality compared with the general population (SAIL SMR=2.64, 95% CI=2.39-2.90, SEER SMR=1.38, 95% CI=1.35-1.42). Patients were more likely to die of CVD compared to the general population regardless of whether they were diagnosed with non-malignant meningiomas subtypes (SAIL SMR=3.13, 95%CI=2.73-3.57; SEER SMR=1.36, 95%CI=1.32-1.40) or malignant gliomas (SAIL SMR=2.08, 95%CI=1.46-2.88; SEER SMR=2.21, 95%CI=2.05-2.38). Patients diagnosed younger than 50 years of age had excess risk from CVD mortality compared to general population than those diagnosed at older ages (SAIL SMR=4.58, 95%CI=2.38-7.84, SEER SMR 2.03-95%CI=1.79-2.03). Patients had greater risk of CVD mortality within the first year after CNS tumour diagnosis in both SAIL and SEER (SMR=2.98, 95% CI=2.39-3.66 &amp; SMR=2.14 95%CI=2.03-2.25, respectively). Conclusion CVD mortality is high among patients diagnosed with CNS tumours compared to general population. Cross national datasets for different histologic types of CNS tumours could help define high risk groups that may be targeted for future prevention and clinical studies to clarify the aetiology of CVD among CNS cancer patients. Citation Format: KAI JIN, Paul Brennan, Michael Poon, Cathie Sudlow, Jonine FIGUEROA. High cardiovascular disease mortality after central nervous system tumor diagnosis: Evidence from UK and USA population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB084.

Trends and Outcomes in the Use of Radiation Therapy and Chemotherapy for the Treatment of Hodgkin's Lymphoma: An Analysis from SEER Database 1985-2014

Background:In the US, there are approximately 8,260 newly diagnosed HL cases and 21,210 death due to HL annually (Siegel et al, Cancer Statistics, 2017). Over the past few decades, a significant survival improvement has been observed due to the advancement in treatment for HL including radiation therapy (RT), multi-agent chemotherapy (CT) regimens and combination of both. However, concerns have been raised due to the risk of late complications from CT and RT, such as pulmonary disease, heart disease and secondary malignancies (Master et al. Anticancer Res. 2017). We aim to investigate whether the use of different treatment modalities are associated with outcome.Methods:Data were extracted from the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 18 program. Patients diagnosed with HL from 1985-2014 were included in this analysis. Demographic information including age, sex, race/ethnicity, annual household income, education and insurance status were also collected. HL is categorized by using International Classification of Disease for Oncology (ICD-O-3) into classical HL NOS (CHL NOS), nodular lymphocyte predominant HL (NLP), lymphocyte rich (LR), mixed cellularity (MC), lymphocyte depleted (LD), and nodular sclerosis (NS). Treatment was categorized into RT alone, CT alone, combination of RT and CT, and no RT or CT. Survival time is calculated by using the date of diagnosis and one of the following dates: date of death, date last known to be alive or date of the study cutoff (December 31, 2014). Chi-square test and Cox regression model was adopted by using SAS 9.4.Exclusion criteria:1) Exclude those with unknown or unspecified race.2) Exclude those patients whose survival was <6 months because time of radiotherapy/chemotherapy was not known to the time of diagnosis.3) Exclude patients with any other type of cancer prior to the diagnosis of HL.4) Exclude patients with second or later primaries, and who were not actively followed.Results:A total 39, 160 patients were included in this analysis. Table 1 shows the Cox regression analysis including adjusted and unadjusted hazard ratios (HRs). Receiving combination modality (both RT and CT) was associated with 45% decreased HR, 95% CI (0.42, 0.70) compared to those who had neither RT or CT. Black race and male patients had a worse survival outcome compared to white race and females, respectively (HR=1.40, HR=1.17). Age was a statistically significant factor associated with increased mortality. Compared to CLH NOS, histology of NS, LC, and NLP were associated with decreased overall mortality (HR=0.84, HR=0.62, HR=0.69, p=0.02) respectively. Stage IV and Stage III were 1.92 and 1.69 times likely to die compared to stage I patients, p<0.01. Those with B symptoms had 48% increased mortality compared to those without, p<0.01. Insured patient had 29% decreased risk of mortality compared to those without insurance, 95% CI (0.54, 0.91). However any Medicaid patients were associated with 36% increased risk of death, 95% CI (1.04, 1.79). Annual household income and education level did not appear to be related to death from HL.Figure 1 illustrates the change of treatment regimen from 1985-2014. An obvious rising was observed in CT from 34.76% to 58.30% from 1985-2014. The percentage among patients who received neither CT nor RT has been stable over the past 30 years. From 1985-2004, we observed that combination modality had been increasing from 16.20% to 37.48%; and after year of 2004, it started to slowly decrease.Table 2 presents the HR of death of patient with HL receiving different treatment modality by year of diagnosis. The HRs were not statistically significant associated with the use of combination modality nor single modality (CT or RT only) from 1985-1999. Among year of diagnosis group 2000-2004, 2005-2009, and 2010-2014, patients with combination modality were associated with 22%, 43% and 44% decreased mortality compared to those who did not have any therapy, respectively (p<0.01).Conclusion:Our results showed that among all HL patients diagnosed between 1985 and 2014, combination modality was associated with decreased mortality. Similar mortality benefit was not observed among patients receiving single modality. Though the use of combination modality has been decreasing over the past 2 decades, a significant lasting survival benefit compared to single modality was still observed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Targeted mass-spectrometry-based assays enable multiplex quantification of receptor tyrosine kinase, MAP kinase, and AKT signaling

SummaryA primary goal of the US National Cancer Institute's Ras initiative at the Frederick National Laboratory for Cancer Research is to develop methods to quantify RAS signaling to facilitate development of novel cancer therapeutics. We use targeted proteomics technologies to develop a community resource consisting of 256 validated multiple reaction monitoring (MRM)-based, multiplexed assays for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. As proof of concept, we quantify the response of melanoma (A375 and SK-MEL-2) and colorectal cancer (HCT-116 and HT-29) cell lines to BRAF inhibition by PLX4720. These assays replace over 60 western blots with quantitative mass-spectrometry-based assays of high molecular specificity and quantitative precision, showing the value of these methods for pharmacodynamic measurements and mechanism-of-action studies. Methods, fit-for-purpose validation, and results are publicly available as a resource for the community at assays.cancer.gov.

Validity and Reproducibility of a Food Frequency Questionnaire to Assess Macro and Micro-Nutrient Intake among a Convenience Cohort of Healthy Adult Qataris.

This study aimed at developing a valid culture-sensitive quantitative food frequency questionnaire (FFQ) for Qatari adults. A convenient sample of healthy Qataris (n = 107) were recruited from family members of Qatar University students. The Diet History Questionnaire II of the US National Cancer Institute was translated to Arabic language, back-translated to English, pilot tested, and then modified accordingly to be used in Qatari setting. Participants were asked to complete the translated version of the FFQ. This FFQ was then validated against three 24 h diet recall (24 hDR) including a weekend day. Participants were asked to complete the FFQ again after one-month period to measure its repeatability. Dietary data were analyzed using the dietary analysis software ESHA. The validity and reliability of FFQ were assessed by comparing the median intake of nutrients and foods and by calculating the Pearson correlation coefficients. The median nutrient intakes assessed by the second FFQ were higher than that reported in the baseline FFQ1 except for fat. The percentage of increase varies between 1.5% and 96%. Results of the second FFQ indicated an overestimation of intake for most nutrients (macro and micro). Macronutrient intakes assessed by the two FFQ and 24 hDR were strongly correlated. The correlation coefficients for micronutrient intakes between FFQ2 and 24hDR were lower than that of the two FFQs except for calcium (r = 0.55) and sodium (r = 0.643). They ranged from (−0.17) for fluorine to (0.643) for sodium. The agreement rates for classifying macronutrient intakes into same or adjacent quartile were between 79.4% and 100% for the two FFQs and between 71% and 100% for the second FFQ and 24hDR. The reported consumption of food groups estimated by FFQ2 was significantly higher than that reported by FFQ1. In conclusion, the developed FFQ was sufficiently valid to assess energy and macronutrients but not micronutrients. The reliability was adequate for most nutrients.

Food Intakes Mediate Ethnic Differences in the Gut Microbiome

ObjectivesGut microbial composition has been associated with diet quality and health outcomes and has also been found to vary across ethnic groups. We explored how ethnic differences in food consumption may mediate some of the ethnic variation in the gut microbiome (GM). MethodsIn a subset of 5,280 Multiethnic Cohort participants, based on a food frequency questionnaire administered in 2003–2008, we assessed overall diet quality using the Healthy Eating Index (HEI-2015; scores 0–100) and specific food consumption using the intake amounts of 10 component food groups used to define common diet quality indexes. GM composition was obtained from 16S rRNA gene sequencing of a stool sample (2013–2016; age 59–98 years) and estimated in genus proportions (as the centered log ratio (CLR) transformed counts). Using mediation analysis, we determined the % of the total ethnicity effect on the genus proportion for each of the ethnically divergent bacterial genera mediated by overall diet quality and component food groups, while adjusting for age, sex, total energy intake, body mass index, and antibiotics use. ResultsOverall diet quality was highest in Whites (mean HEI-2015 = 73.1) and African Americans (72.7), followed by Japanese Americans (71.3), Native Hawaiians (70.1) and Latinos (68.9). Of the 152 genera, 7 with the largest ethnic variation (CLR difference for the genus between most vs. least abundant ethnic group > 1) were examined for mediation. Five genera showed significant mediation of their ethnic differences through diet (P < 0.00,045 for Bonferroni correction), ranging from the –12% for Flavonifractor in African Americans vs. Whites mediated by vegetable intake to the 19% for Christensenellaceae R-7 group in Latinos vs. Whites mediated by overall diet quality. Large mediation effects were also seen by saturated fat for Ruminococcaceae NK4A214 in African Americans vs. Whites (18%) and by alcohol for Erysipelatoclostridium in Latinos vs. Whites (18%). ConclusionsOverall diet quality and component foods may contribute substantially to ethnic differences in gut bacterial composition. These novel findings may help the development of targeted dietary interventions to improve the gut health of specific ethnic groups. Funding SourcesThis work was supported by the US National Cancer Institute (NCI) grants P01 CA168530, U01 CA164973, and P30 CA71789.

Association of inoperable glioblastoma with a heterogeneous functional and survival outcome.

e14036 Background: “Biopsy only” GBM patients is an understudied group of patients associated to a poor outcome, which has been reported to represent 21% of histologically confirmed GBM in the US National Cancer Data Base. Pattern of care included radiotherapy-temozolomide (RT-TMZ) standard regimen completed in 15% of patients, any other form of oncologic treatment in 60%, and supportive care alone in 25% of patients (Kole, Cancer 2016). Our objective was to explore heterogeneity of inoperable GBM patients group, both for patients characteristics, pattern of care planned and completed, functional and survival outcome. Methods: Patients with inoperable GBM included in a prospective regional glioma cohort initiated in 2014 were retrospectively reviewed for patients characteristics, MRI finding, treatment allocation and delivery. Functional independency analyzed as a cumulative time of KPS≥70, PFS and OS were analyzed. Results: Of 535 patients referred to our center, 449 patients were included at initial surgery, of which 158 patients (35%) underwent biopsy only. 18 patients were excluded for missing data leaving 139 patients for the present analysis. 54 (39%) were referred to RT-TMZ (50 patients completed concomitant treatment), 68 (49%) considered unfitted for RT received chemotherapy upfront (CT-UF) (of which 3 were subsequently referred to RT), 17 (12%) referred to palliative care only (PC). Groups differed at baseline for age (mean 60, 68, 69y for RT-TMZ, CT-UF, PC respectively); for KPS (70, 60, 50 for RT-TMZ, CT-UF, PC respectively); for mean tumor surface (793, 1420, 1412 cm2 for RT-TMZ, CT-UF, PC); for tumor extension (bilateral in 6.4% and 29.3% for RT-CT and CT-UF respectively); for steroid intake (45, 60, 100 mg daily respectively). Median OS was 14 months (95% CI, 9.65-18.71), 8 months (95% CI, 4.62-7.67), 2 months (95% CI, 0.67-3.33) for RT-TMZ, CT-UF, PC respectively. Of importance, mean duration of functional independence was of 8.3 months, 2.1 months, and 0.1 month for RT-TMZ, CT-UF, and PC respectively; 33/139 (24%) of the patients experienced functional independency for more than 40% of their life time. Conclusions: Inoperable GBM constitute a large and heterogeneous population in which more than 1/3 of the patients are amenable to standard of care, with survival outcome similar to the one of patients who underwent surgery. Patients considered unfit for RT-CT at diagnosis fail to be referred subsequently to RT after CT and exhibit a poor survival outcome that deserve new effective treatments. Cumulative duration of functional independence is limited and should be considered as part of treatment evaluation.

Trends in glassy cell cervical cancer in the United States from 1973-2015: Analysis based on SEER database.

e17502 Background: Glassy cell carcinoma of cervix (GCCC) is a rare histological subtype of cervical cancer which has historically been associated with rapidly progressive disease, early development of metastases and overall poor prognosis. We attempt to define real-world trends in GCCC in the United States based on data from SEER (Surveillance, Epidemiology and End Results) database. Methods: We extracted data from the US National Cancer Institute's SEER 2018 dataset using ICD-O code for ‘Cervix Uteri Glassy Cell Carcinoma’. All patients who were diagnosed between 1973-2015 were included. Statistical analysis was done using SPSS 26. Kaplan Meier curve was used for survival analysis. Results: Data for a total of 57 patients with GCCC was available from 1975 to 2017. Median age at diagnosis was 38 years (range 30.5-44.5). Increased frequency of cases was noted in white females (77.2%) as compared to black population (22.2%). Most cases initially presented with localized or regional spread (47.4% and 40.4% respectively) with distant metastasis seen in only 10.5% patients. Data analysis revealed that 63.2% patients had Grade III poorly differentiated carcinoma, 66.7% received radiation therapy, 57.9% underwent chemotherapy and 59.6% had cancer direceted surgery performed. Calculated mean overall survival was 121.9 months. We were unable to calculate 5 year and 10 year median overall survival due to small sample size and censored data. Conclusions: GCCC is a rare histologic type of cervical cancer that presents at a younger age, is more frequently seen in white females and is commonly associated with localized or regional spread at time of initial presentation.[Table: see text]

Impact of positive surgical margins on survival after partial nephrectomy in localized kidney cancer: analysis of the National Cancer Database.

BACKGROUND The impact of positive surgical margins (PSM) on outcomes in partial nephrectomy (PN) is controversial. We investigated impact of PSM for patients undergoing PN on overall survival (OS) in different stages of renal cell carcinoma (RCC). METHODS Retrospective analysis of patients from the US National Cancer Database who underwent PN for cT1a-cT2b N0M0 RCC between 2004-13. Patients were stratified by pathological stage (pT1a, pT1b, pT2a, pT2b, and pT3a [upstaged]) and analyzed by margin status. Cox Regression multivariable analysis (MVA) was performed to investigate associations of PSM and covariates on all-cause mortality (ACM). Kaplan-Meier analysis (KMA) of OS was performed for PSM versus negative margin (NSM) by pathological stage. Sub-analysis of Charlson Comorbidity Index 0 (CCI=0) subgroup was conducted to reduce bias from comorbidities. RESULTS We analyzed 42,113 PN (pT1a: 33,341 [79.2%]; pT1a, pT1b: 6689 [15.9%]; pT2a: 757 [1.8%]; pT2b: 165 [0.4%]; and pT3a: upstaged 1161 [2.8%]). PSM occurred in 6.7% (2823) (pT1a: 6.5%, pT1b: 6.3%, pT2a: 5.9%, pT2b: 6.1%, pT3a: 14.1%, P<0.001). On MVA, PSM was associated with 31% increase in ACM (HR 1.31, P<0.001), which persisted in CCI=0 sub-analysis (HR: 1.25, P<0.001). KMA revealed negative impact of PSM vs. NSM on 5-year OS: pT1 (87.3% vs. 90.9%, P<0.001), pT2 (86.7% vs. 82.5%, P=0.48), and upstaged pT3a (69% vs. 84.2%, P<0.001). CONCLUSIONS PSM after PN was independently associated with across-the-board decrement in OS, which worsened in pT3a disease and persisted in sub-analysis of patients with CCI=0. PSM should prompt more aggressive surveillance or definitive resection strategies.

Transarterial radioembolization versus systemic treatment for hepatocellular carcinoma with macrovascular invasion: Analysis of the US National Cancer Database.

Background and Aims: Systemic therapy remains the recommended first-line treatment for hepatocellular carcinoma (HCC) with macrovascular invasion (MVI). Transarterial radioembolization (TARE) is a promising alternative treatment given superior quality of life. The aims of this study were to 1) characterize trends and correlates for TARE as first-line treatment of HCC patients with MVI in the US and 2) compare survival after TARE versus systemic therapy. Methods: We used the US National Cancer Database to identify patients with T3BN0M0 HCC during 2010-2017. We performed multivariable logistic regression to identify factors associated with use of TARE vs. systemic therapy and Cox proportional hazards regression to identify factors associated with overall survival. Results: Of 11,259 patients with T3BN0M0 HCC, 1454 (12.9%) and 3915 (34.7%) patients were treated with TARE and systemic therapy, respectively. The proportion of patients who received TARE increased from 13.0% in 2010 to 37.0% in 2017. Older age, White race, and receiving care at an academic cancer program were associated with receipt of TARE, while lack of insurance, higher MELD score, Charlson comorbidity Index ≥3, and Northeast region were associated with receipt of systemic therapy. TARE was associated with reduced mortality compared to systemic therapy (adjusted hazard ratio: 0.74, 95%CI: 0.68-0.80), with consistent results observed in propensity weighted analysis and across all examined subgroups. Conclusion: Use of TARE as first-line therapy for HCC with MVI has increased in the US. Patient characteristics, region, and medical center type affected the use of TARE. TARE was associated with reduced mortality compared to systemic therapy for HCC patients with MVI.

Meatable raises cash for cell-based meat

The Dutch start-up Meatable has raised $47 million in its first round of funding from investors to advance its cultivated-meat technology. Backers include DSM Venturing and Rick Klausner, former head of the US National Cancer Institute and of global health at the Bill and Melinda Gates Foundation. Meatable says its process efficiently grows cow and pig muscle and fat cells that mature in a few weeks. The company will use the funds to bring its first products to market.