Newly-diagnosed Cancer Research Articles

Home-based aerobic exercise feasibility in oxaliplatin-receiving newly-diagnosed cancer survivors

PurposePhysical activity (PA) is beneficial but difficult to maintain during chemotherapy. This pilot RCT explored the feasibility of the MI-Walk intervention—an 8-week motivational enhancement therapy- and home-based brisk walking intervention—among gastrointestinal (GI) cancer survivors receiving chemotherapy. MethodsSixty stage II-IV GI cancer survivors were recruited from 5 sites at their second infusion visit. Participants were randomized to receive PA education alone or the MI-Walk intervention: motivational enhancement therapy consisting of 3 motivational interviewing and self-efficacy-enhancing counseling sessions, a Fitbit Charge 2, exercise diaries, telephone follow-up, scripted motivational email messages, and optional weekly walking groups. ResultsThe enrollment and completion rates were 62% and 90%, respectively. The MI-Walk participants (n = 29; mean age = 56.79, SD = 11.72; 97% white; 79% male) reported a baseline moderate-vigorous PA duration of 250.93 (SD = 636.52) min/wk. The mean MI-Walk Intervention acceptability score was 50.32 (SD = 12.02) on a scale of 14–70. Mean Fitbit and counseling helpfulness scores on a 5-point scale were 3.67 (SD = 1.43) and 3.44 (SD = 1.36), respectively. Participants’ Fitbit moderate-vigorous PA 8-week averages ranged from 0 to 716.88 min/wk; 64% of participants adhered to ≥127 min/wk. Several characteristics (e.g., age, comorbidity, PA level, employment status, BMI, education level, gender, symptoms) were associated with enrollment, attrition, and intervention acceptability and adherence (p < 0.05). ConclusionEnrollment and retention were adequate. The Fitbit and counseling were the most helpful. Acceptability and adherence varied based on participant characteristics; therefore, intervention tailoring and further research among cancer survivors less physically active at baseline and most in need of complex exercise intervention are needed.ClinicalTrials.gov NCT03515356.

The incidence and risk factors of newly-diagnosed cancer after diagnosis of venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background/Introduction Venous thromboembolism (VTE) may be the earliest sign of cancer, although there are no established screening strategies for occult cancer. This could be partly due to lack of the real-world incidence and risk factors of occult cancer after diagnosis of VTE in the current era. Purpose The current study aimed to evaluate clinical characteristics and outcomes between patients who were newly diagnosed with cancer after diagnosis of VTE and those who were not, and investigate incidence and risk factors of newly-diagnosed cancer after diagnosis of VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population was consisted of 3706 patients without known active cancer at diagnosis of VTE, who were divided into patients with newly-diagnosed cancer after diagnosis of VTE (N=250, 6.7%) and those without (N=3456, 93.3%). To explore risk factors of newly-diagnosed cancer, we constructed the multivariable Cox proportional hazard model which consisted of variables with P values &amp;lt;0.05 in univariate analysis. Results The cumulative incidences of newly-diagnosed cancer were 1.5% at 30-day, 3.7% at 1-year, 7.0% at 3-year, 11.1% at 5-year, and 16.0% at 7-year. The most common types of newly-diagnosed cancer was colon (17.2%), followed by lung (14.8%) and blood (8.0%). Patients with newly-diagnosed cancer were older (71.6 vs. 67.2 years, P&amp;lt;0.001) and had lower body mass index (22.9 vs. 23.8 kg/m2, P=0.004) than those without. Patients with newly-diagnosed cancer more frequently had several comorbidities such as history of cancer (35% vs. 11%, P&amp;lt;0.001), hypertension (51% vs. 44%, P=0.04), diabetes mellitus (21% vs. 16%, P=0.03), and autoimmune disorder (20% vs. 13%, P=0.004), whereas they less frequently had transient provoking risk factors for VTE (29% vs. 39%, P&amp;lt;0.001). The cumulative incidence of all-cause death was significantly higher in patients with newly-diagnosed cancer than those without (59.3% vs. 21.0% at 7-year). The multivariable Cox proportional hazard model revealed that old age (hazard ratio [HR]: 1.02 per 1 year [1.01-1.03], P&amp;lt;0.001), history of cancer (HR: 3.60 [2.75-4.67], P&amp;lt;0.001), autoimmune disorder (HR: 1.51 [1.09-2.05], P=0.01), and absence of transient provoking risk factors for VTE (HR: 1.36 [1.03-1.80], P=0.03) were independently associated with newly-diagnosed cancer after diagnosis of VTE. Conclusions In the current era, the incidence of newly-diagnosed cancer was 3.7% at 1-year with initial acute increase followed by continuous increase, and several independent risk factors were identified, which might be useful for consideration of optimal screening strategies for occult cancer based on individual risk.Newly-diagnosed cancer

Clinical and Demographic Characteristics, Mechanisms, and Outcomes in Patients With Acute Ischemic Stroke and Newly Diagnosed or Known Active Cancer.

Patients with a new diagnosis of cancer carry an increased risk of acute ischemic stroke (AIS), and this risk varies depending on age, cancer type, stage, and time from diagnosis. Whether patients with AIS with a new diagnosis of neoplasm represent a distinct subset from those with a previously known active malignancy remains unclear. We aimed to estimate the rate of stroke in patients with newly diagnosed cancer (NC) and previously known active cancer (KC) and to compare the demographic and clinical features, stroke mechanisms, and long-term outcomes between groups. Using 2003-2021 data from the Acute STroke Registry and Analysis of Lausanne registry, we compared patients with KC with patients with NC (cancer identified during AIS hospitalization or within the following 12 months). Patients with inactive and no history of cancer were excluded. Outcomes were the modified Rankin scale (mRS) score at 3 months and mortality and recurrent stroke at 12 months. We used multivariable regression analyses to compare outcomes between groups while adjusting for important prognostic variables. Among 6,686 patients with AIS, 362 (5.4%) had active cancer (AC), including 102 (1.5%) with NC. Gastrointestinal and genitourinary cancers were the most frequent cancer types. Among all patients with AC, 152 (42.5%) AISs were classified as cancer related, with nearly half of these cases attributed to hypercoagulability. In multivariable analysis, patients with NC had less prestroke disability (adjusted odds ratio [aOR] 0.62, 95% CI 0.44-0.86) and fewer prior stroke/transient ischemic attack events (aOR 0.43, 95% CI 0.21-0.88) than patients with KC. Three-month mRS scores were similar between cancer groups (aOR 1.27, 95% CI 0.65-2.49) and were predominantly driven by the presence of newly diagnosed brain metastases (aOR 7.22, 95% CI 1.49-43.17) and metastatic cancer (aOR 2.19, 95% CI 1.22-3.97). At 12 months, mortality risk was higher in patients with NC vs patients with KC (hazard ratio [HR] 2.11, 95% CI 1.38-3.21), while recurrent stroke risk was similar between groups (adjusted HR 1.27, 95% CI 0.67-2.43). In a comprehensive institutional registry spanning nearly 2 decades, 5.4% of patients with AIS had AC, a quarter of which were diagnosed during or within 12 months after the index stroke hospitalization. Patients with NC had less disability and prior cerebrovascular disease, but a higher 1-year risk of subsequent death than patients with KC.

The essential roles of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis.

Hematopoietic stem cells (HSCs) developing from mesoderm during embryogenesis are important for the blood circulatory system and immune system. Many factors such as genetic factors, chemical exposure, physical radiation, and viral infection, can lead to the dysfunction of HSCs. Hematological malignancies (involving leukemia, lymphoma, and myeloma) were diagnosed in more than 1.3 million people globally in 2021, taking up 7% of total newly-diagnosed cancer patients. Although many treatments like chemotherapy, bone marrow transplantation, and stem cell transplantation have been applied in clinical therapeutics, the average 5-year survival rate for leukemia, lymphoma, and myeloma is about 65%, 72%, and 54% respectively. Small non-coding RNAs play key roles in a variety of biological processes, including cell division and proliferation, immunological response and cell death. With the development of technologies in high-throughput sequencing and bioinformatic analysis, there is emerging research about modifications on small non-coding RNAs, as well as their functions in hematopoiesis and related diseases. In this study, we summarize the updated information of small non-coding RNAs and RNA modifications in normal and malignant hematopoiesis, which sheds lights into the future application of HSCs into the treatment of blood diseases.

HIV Screening among Patients with Newly Diagnosed Solid and Hematologic Malignancies in a Tertiary Hospital in the Philippines.

This preliminary study determined the prevalence of HIV infection among patients with newly diagnosed solid and hematologic malignancies at the Philippine General Hospital - Cancer Institute. Adult Filipinos aged 19 years and above with biopsy- or imaging-confirmed malignancy and for chemotherapy, seen at the adult medical oncology and hematology clinic from January to September 2021 were included. Demographic and clinical data were obtained using a questionnaire. Rapid HIV screening was performed using blood extracted via finger prick. Pre- and post-test counselling were conducted. Of the 124 patients included in our study, majority were female (91, 73.4%), and 45 years old and above with a median age of 49 (20 - 74). Majority had solid tumors (121, 97.6%) with breast cancer being the most common (67, 54.0%) followed by colorectal (18, 14.5%), and head and neck cancer (14, 11.3%). Among those with hematologic malignancies, two had acute myelogenous leukemia and one had multiple myeloma. Six patients had AIDS-defining malignancies (NHL, cervical cancer). HIV risk factors and associated conditions were present in 18 patients (14.5%). Ten patients reported prior HIV testing. None of the patients tested positive for HIV. The absence of HIV cases detected in our cohort may be due to the low prevalence of HIV risk factors and associated conditions. At this time, there is insufficient evidence to routinely recommend HIV testing among newly-diagnosed cancer patients. However, physicians are encouraged to offer HIV testing to cancer patients, especially to those with HIV risk factors, given the benefits of early detection and management of HIV.

Impact of wallet cards compared to conventional chemotherapy education in patients with newly-diagnosed cancer.

363 Background: According to American Cancer Society, 1.9 million new cases of cancer were diagnosed in year 2021, majority of who will undergo chemotherapy (1). With these treatments, there is often an overwhelming amount of information given to patients. We will first assess the percentage of new cancer patients that can recall their cancer treatments with the current patient education format. We then aim to improve patient understanding of their treatment with the introduction of a chemotherapy wallet card. Methods: This is a single center prospective cohort study at the University of Louisville, Brown Cancer Center. In phase one 50 new patients will be recruited from various oncology clinics who will receive conventional verbal chemotherapy education. On cycle two of their treatment, we will administer a survey (figure 1) to assess their understanding of their regimen. In phase two we will recruit 50 new patients and introduce a chemotherapy wallet card filled by the pharmacist to be given during their chemotherapy education and administer the survey on cycle two. We will then compare these two populations to evaluate the impact of the chemotherapy wallet cards. Results: Preliminary results from the first phase have been obtained of 15 newly diagnosed cancer patients. Surveys obtained on cycle two revealed 100% patients correctly identified their cancer diagnosis and 60% were able to correctly name their chemotherapy regimen. 53% of patients were able to identify three correct treatment side effects. Conclusions: Preliminary results show 60% of patients have suboptimal identification of their chemotherapy regimens. Previous studies have shown many patients will visit the emergency department in their first year of treatment. This is of concern as patients may not be able to provide accurate information of their current treatment to these providers resulting in suboptimal care. Our goal will be to see if chemotherapy wallet cards will help to increase patient knowledge and improve patient quality of care.[Table: see text]

Correlation of Inflammation and Coagulation Markers with the Incidence of Deep Vein Thrombosis in Cancer Patients with High Risk of Thrombosis.

BackgroundDeep vein thrombosis (DVT) is a common complication and the second leading cause of death in cancer patients. Pro-inflammatory stimuli in the cancer microenvironment induce nuclear factor kappa B (NF-κB) signaling pathway that plays an integral role in immunothrombosis mechanism.ObjectiveTo investigate the role of inflammatory and coagulation biomarkers in the development of DVT in cancer patients with high risk of thrombosis (Khorana score ≥2).Subjects and methodsThis study was a cross-sectional study at Dr. Kariadi General Hospital. The serum levels of proinflammatory cytokines, ie, NF-κB, interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and coagulation biomarkers, ie, tissue factor (TF), prothrombin fragment F1+2 (F1+2), fibrinogen and D-dimer were measured in newlydiagnosed cancer patients with a highrisk of thrombosis. Color duplex sonography was used for DVT screening.ResultsFrom January to November 2021, there were 83 eligible patients. DVT was confirmed in 8 subjects (9.63%). Univariate analysis revealed a significant difference between the median age of patients with DVT compared to non-DVT patients, 49.5 years (range: 23–60 years) and 42 years (range: 19–60 years), with p=0.046. D-dimer level was higher in DVT patients [(6.020 µg/L, range 2.090–20.000) vs (1.940 µg/L, range 270–20.000), p=0.005]. Multivariate analysis revealed age and D-dimer were significantly correlated with DVT incidence. In all patients, there were significant positive correlations between several inflammatory and coagulation activation parameters, which were IL-6 with D-dimer and F1+2, CRP with F1+2 and D-dimer as well as TNF-α with F1+2. However, these findings were not shown in DVT patients.ConclusionIn cancer patients with a high risk of thrombosis, age and D-dimer level are the significant variables towards the incidence of DVT. In patients with DVT, there was no significant correlation between inflammatory and coagulation activation parameters.

Abstract 714: Weight changes between one year before and following breast cancer diagnosis in relation to mTOR protein expression in tumor tissues in the Women’s Circle of Health Study

Abstract Background: Obesity is an important prognostic factor for breast cancer. Aberrant activation of the mechanistic Target of Rapamycin (mTOR) pathway is associated with obesity, cross-sectionally, as well as with breast cancer survival. This study aimed to examine the association of weight change between one year before and following cancer diagnosis with a panel of mTOR protein markers in breast tumors. The study hypothesis was that greater weight gain compared to less or no weight gain would be associated with higher mTOR protein expression in breast tumors. Methods: Study participants were 698 newly-diagnosed breast cancer cases (545 Black women and 153 White women) from the Women’s Circle of Health Study (WCHS). Surgical tissue microarrays were stained for mTOR, phosphorylated mTOR, phosphorylated AKT, and phosphorylated P70S6K using immunohistochemistry. In-home interviews were conducted approximately 10 months after breast cancer diagnosis, and anthropometric measurement was taken by trained staff. Participants reported body weight one year before the diagnosis, excluding the time of pregnancy or nursing. Linear regression analyses were conducted to estimate percent differences in protein expression across quartiles of weight change, adjusting for age, race, BMI one year before diagnosis, menopausal status, history of diabetes, and molecular tumor subtype. Results: Study participants had a mean age of 52.7 (SD = 10.8) years and BMI one year before diagnosis of 30.7 (SD = 6.9) kg/m2. The proportions of participants who had loss ≥5 lbs, loss &amp;lt;5 lbs, no change to gain &amp;lt;5 lbs, and gain ≥5 lbs in weight were 33.7%, 16.2%, 16.2%, and 33.7%, respectively. The fourth vs. first quartile of the weight change was associated with a higher protein expression of mTOR (35.3%, 95% CI = 3.8%, 76.5%), and there was a dose-response pattern (P-trend = 0.0273). No associations were observed between weight change and phosphorylated protein expression. Conclusion: Short-term weight gain before breast cancer diagnosis and following diagnosis may play a role in breast tumor mTOR protein expression. Our findings warrant validation in a study with a prospective measurement of weight gain before breast cancer surgery. Citation Format: Mmadili N. Ilozumba, Angela R. Omilian, Song Yao, Weizhou Zhang, Susmita Datta, Warren Davis, Chi-Chen Hong, Elisa V. Bandera, Thaer Khoury, Christine B. Ambrosone, Ting-Yuan David Cheng. Weight changes between one year before and following breast cancer diagnosis in relation to mTOR protein expression in tumor tissues in the Women’s Circle of Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 714.

Abstract 3219: Changes and intra-individual reliability in computed tomography image-assessed adiposity and skeletal muscles areas after breast cancer surgery

Abstract Background: Levels of adiposity and skeletal muscles are prognostic indicators in breast cancer patients; however, data are limited on temporal changes in body composition, particularly in different densities of muscles, before and after mastectomy. Objectives: We examined the change in CT-assessed adipose tissue and different density of skeletal muscle areas using a high-resolution segmentation method in breast cancer patients before and after surgery. Methods: This study included 50 newly-diagnosed breast cancer patients who had taken CT scans before and after surgery. We analyzed their third lumbar (L3) CT images to measure the areas of adipose tissue and five-level (from very-high-density to very-low-density) skeletal muscle components. We assessed mean and percent changes in areas using paired t-test and calculated the intra-class correlation (ICC). Results: Patients’ mean age at diagnosis was 58.3 (SD=12.5) years. The mean duration between scans was 591 (SD=537) days. There was a significant decrease in the areas of subcutaneous adipose tissue (mean change= -36.17 cm2, 11.72% decrease, p=0.029), total adipose tissue (mean change= -45.64 cm2, 10.18% decrease, p=0.032), and very-high-density muscle (mean change= -0.37 cm2, 11.08% decrease, p=0.010). The ratio of total adipose tissue and total skeletal muscle decreased from 3.67 to 3.32 after surgery (mean change= -0.36, 9.81% decrease, p=0.061). There was a strong correlation in adipose tissues and skeletal muscle areas of pre-and post-surgery scans taken within 3 years apart (ICC=0.802 to 0.999, all p&amp;lt;0.05), but the correlations were attenuated in scans taken &amp;gt;3 years apart (ICC = -0.055 to 0.738, all p&amp;gt;0.05). Conclusion: In this sample of breast cancer patients who have undergone surgery, there was a significant decrease in subcutaneous adipose tissues, total adipose tissues, and very-high-density muscle areas over time. Body composition assessed by CT images is reliable for a 3- year period involving breast cancer surgery. These findings serve as a baseline for prospective studies examining the impact of these changes on breast cancer outcomes. Keywords: Adipose tissue, skeletal muscle, computed tomography scans, breast cancer, surgery Citation Format: Livingstone Aduse-Poku, Dheeraj Gopireddy, Mauricio Henandez, Chandana Lall, Joel Divaker, Sara Falzarano, Shahla Masood, Weizhou Zhang, Susmita Datta, Jiang Bian, Ting-Yuan David Cheng. Changes and intra-individual reliability in computed tomography image-assessed adiposity and skeletal muscles areas after breast cancer surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3219.

Abstract 5064: Patient-specific forecasting of prostate cancer growth during active surveillance using an imaging-informed mechanistic model

Abstract Active surveillance (AS) is a suitable management option for many newly-diagnosed prostate cancer (PCa) cases, which usually exhibit low to intermediate clinical risk. In AS, patients are closely monitored via multiparametric magnetic resonance imaging (mpMRI), prostate-specific antigen tests, and biopsies until these reveal an increase in PCa risk that warrants treatment. Thus, AS can contribute to reduce the current overtreatment of PCa and avoid treatment side-effects that may adversely impact patients’ lives without necessarily improving their longevity. However, current AS protocols rely on assessing PCa according to population-based studies, which complicates the design of personalized monitoring plans and the early detection of tumor progression. To address these issues, we propose to predict PCa growth using patient-specific forecasts based on an mpMRI-informed mechanistic model. Here, we present a preliminary study in a cohort of seven PCa patients who enrolled in AS and had three mpMRI scans over a period of 1.4 to 4.9 years. Our mechanistic model describes PCa growth in terms of tumor cell density dynamics, consisting of mobility and proliferation modeled via a diffusion process and a logistic law, respectively. We segment each patient’s prostate geometry on T2-weighted images and estimate tumor cell density from standard apparent diffusion coefficient (ADC) maps. To facilitate PCa modeling, we co-register each patient’s mpMRI datasets with a biomechanical elastic method that aligns the prostate segmentations across the imaging datasets. The model is initialized with the data from the first mpMRI scan. Model calibration relies on a nonlinear least-squares algorithm that minimizes the mismatch between ADC-measured and model-predicted tumor cell density at the second mpMRI date. For validation, we initialize the patient-specific calibrated model with the second mpMRI dataset and forecast PCa growth at the third mpMRI date, which we compare to the corresponding ADC-estimated tumor cell density. Model calibration resulted in a concordance correlation coefficient (CCC) &amp;gt; 0.99 for both tumor volume and global tumor cell count across the cohort. For each patient, the spatial fit of tumor cell density at the second scan date rendered a median Dice score and CCC of 0.79 and 0.52, respectively. Model validation resulted in CCCs of 0.88 and 0.81 for tumor volume and global tumor cell count across the cohort. Comparing the patient-specific ADC-estimated and model forecasts of tumor cell density at the third scan date, we obtained a median Dice score and CCC of 0.65 and 0.46, respectively. Thus, while improvement and further testing in larger cohorts are still needed, these results do suggest that our computational forecasting approach is a promising technology to predict the spatiotemporal growth of PCa during AS on a patient-specific basis. Citation Format: Guillermo Lorenzo, Jon S. Heiselman, Michael A. Liss, Michael I. Miga, Hector Gomez, Thomas E. Yankeelov, Thomas J. Hughes, Alessandro Reali. Patient-specific forecasting of prostate cancer growth during active surveillance using an imaging-informed mechanistic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5064.

Parental informed consent comprehension in childhood cancer clinical trials: Associations with social determinants of health.

6512 Background: Adequate informed consent (IC) comprehension is an ethical right prior to participation in clinical trials. Research investigating IC comprehension and associations with social determinants of health (SDoH) is lacking. We assessed whether SDoH and related contextual factors were associated with parental IC comprehension in therapeutic childhood cancer clinical trials. Methods: We prospectively enrolled parents of children with newly-diagnosed cancer. Univariable and multivariable regression were used to assess whether objective IC comprehension and related domains ( Purpose/Procedures/Randomization, Risks/Benefits, Alternatives, and Voluntariness) were associated with SDoH (ethnicity, marital status, language, education attainment, employment, insurance, socio-economic status, health literacy [HL]) and contextual factors (cancer type, voluntariness, satisfaction with IC). Results: Of 223 parents included, 112 (50%) were Hispanic and 38% of Hispanics were monolingual Spanish-speaking. In adjusted multivariable analyses, limited HL was significantly associated with lower overall IC comprehension (β = -7.22; 95% CI, -10.9 to -3.59; P &lt; 0.001) and lower comprehension of Purpose/Procedures/Randomization (β = -7.53; 95% CI, -11.3 to -3.73; P &lt; 0.001), Risks/Benefits (β = -8.14; 95% CI, -15.5 to -0.772; P = 0.031), and Alternatives (β = -17.0; 95% CI, -30.5 to -3.57; P = 0.013). Preferred Spanish language of written/verbal medical information was significantly associated with lower comprehension of Purpose/Procedures/Randomization (β = -8.50; 95% CI, -15.1 to -1.89; P = 0.012) and Voluntariness (β = -20.1; 95% CI, -34.9 to -5.33; P = 0.008). Lower satisfaction with informed consent (β = 0.988; 95% CI, 0.460 to 1.52; P &lt; 0.001) and single marital status (β = -4.42; 95% CI, -7.81 to -1.02; P = 0.011) were significantly associated with lower IC comprehension. Conclusions: Among parents of children with newly diagnosed cancer who provided consent for their child’s participation in a therapeutic clinical trial, limited HL was consistently associated with lower IC comprehension in all domains analyzed, except for Voluntariness. Spanish language preference for medical information was associated with lower comprehension of two domains; and lower satisfaction was associated with lower overall IC comprehension. These findings suggests that parents with limited HL, limited English-proficiency, and lower satisfaction may not fully comprehend the IC and thereby not truly make informed decisions. Our findings highlight the potential role of language-concordant interventions tailored to the participant’s HL level in order to ultimately improve IC comprehension and contribute to a reduction of disparities in clinical trial participation and promote equitable translation of discoveries and treatments to underserved groups.

Long-term survival in newly-diagnosed ovarian cancer patients.

e17543 Background: A proportion of women with ovarian cancer, even those with advanced-stage disease, will experience long-term survival post diagnosis. Mixture cure modeling provides insight into factors related to both short-term recurrence and death as well as long-term survival. The goals of this study were to estimate the long-term survival rate, and to evaluate associations between patient characteristics and the long-term survival rate and landmark 5- and 10- year survival, in a sample of newly-diagnosed ovarian cancer patients. Methods: The Tempus EMR dataset contains patients from academic &amp; community oncology centers in the U.S. This study included adult women with a new primary diagnosis of ovarian, fallopian tube, or peritoneal cancer between 2000 and 2020. Women treated with a poly-ADP ribose polymerase inhibitor (PARPi), pembrolizumab, or nivolumab were excluded (n = 947; final sample size = 6,598). Mixture cure models were used to estimate the long-term survival rate (probability of living as long as an age- and gender-matched person without ovarian cancer), overall and stratified by patient demographic &amp; clinical characteristics. Relative importance of variables associated with long-term survival was evaluated using logistic regression models with 5- and 10-year landmark outcomes. Results: Younger age, earlier stage, lower grade, favorable ECOG score, and platinum sensitivity were associated with better overall survival (OS). The long-term survival rate in our model was 25.0% (95% CI: 21.5-28.9). The long-term survival rate was higher for age &lt; 65 vs. age 75+ [29.0% (24.8-33.6) vs. 10.5% (2.9-31.6)], early vs. advanced stage disease [62.0% (41.4-78.9) vs. 17.8% (14.1-22.2)], grade 1-2 vs. 3-4 [31.4% (12.1-60.3) vs. 20.4% (14.6-27.8)], ECOG 0-2 vs. 3-4 [26.1% (21.4-31.3) vs. 2.6% (0.05- 56.5)], and platinum sensitive vs. platinum resistant patients [47.5% (43.1-51.9) vs. 9.4% (7.0-12.5)]. Analyzing 5- and 10-year landmarks [n = 3,944 (59.8%), n = 3,107 (47.1%), respectively] in multivariable logistic regression models, platinum sensitivity had the strongest association, followed by cancer stage. Conclusions: Understanding differences in long-term survival based on patient characteristics is important for clinical decision-making and personalizing treatment. Overall, one quarter of ovarian cancer patients were long-term survivors; long-term survivors were more likely to be younger and have earlier stage disease, low grade disease, better performance status, or sensitivity to platinum-based therapy. These results also provide a baseline to evaluate long-term survival in patients on newer therapies such as PARPi when sufficient follow-up data are available.

Theory-guided assessment of barriers and facilitators to adequate informed consent for childhood cancer clinical trials: Using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework.

6539 Background: To participate in childhood cancer clinical trials, parents/legal guardians must provide informed consent (IC), which is a fundamental ethical right. However, barriers to achieving valid IC include: use of medical jargon, misunderstanding about clinical trials procedures, tremendous emotional distress surrounding the initial cancer diagnosis, and the complexity and length of the IC forms. There are scarce data on using theory to assess perspectives of parents of children with cancer on barriers and facilitators for adequate IC in diverse populations. Methods: Using implementation science theory and methods, we assessed parent-reported barriers and facilitators to adequate IC, in a convenience sample that included a significant number of Hispanics. Twelve qualitative semi-structured interviews and 224 open-ended surveys were conducted with 236 parents of children with newly-diagnosed cancer at Rady Children’s Hospital-San Diego, a large quaternary children’s hospital in California. Fifty-three percent of participants were Hispanic and 38% were monolingual Spanish-speakers. We utilized the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework, specifically domains of outer context, inner context, bridging and innovation factors. Four main codes (IC concepts and delivery; desired clinical trial information; motivations and emotions related to clinical trial enrollment; and potential areas for interventions) were used as a coding guide for analysis. Interviews and surveys were transcribed and coded for thematic analysis by three independent coders to identify key barriers and facilitators. Results: Four main themes were identified as barriers: 1) Complexity of the IC forms and discussion (lengthy, confusing, not available in Spanish, and use of medical jargon); 2) parents feeling emotionally overwhelmed, anxious and pressured around the IC; 3) parents viewing the clinical trial as the only treatment option; and 4) mistrust and fear of clinical trial procedures. Four IC facilitators were identified: 1) simpler explanations of study procedures; 2) provider flexibility for accommodations when delivering the IC, including psychosocial support; 3) active promotion of voluntariness and trust; and 4) supplemental education in lay language, including request for peer-education, decision aids, and navigation to “bridge the provider-patient gap.” Conclusions: Our implementation science approach identified multiple barriers and facilitators to adequate IC in a diverse sample of parents. Findings can inform potential interventions to enhance IC for childhood cancer clinical trials, including the use of decision aids, peer-navigation, and interventions tailored to the language and culture of the individual.

Prognostic impact of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers in esophageal or gastric cancer patients with hypertension - a real-world study

BackgroundAngiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are used in treating cardiovascular diseases. Previous studies indicated that ACEIs/ARBs may benefit cancer patients by inhibiting tumor angiogenesis and proliferation. The effect of ACEIs/ARBs on cancer survival in esophageal and gastric cancer is still unclear. This study is to investigate the association between ACEIs/ARBs usage and esophageal and gastric cancer prognosis.MethodsThis retrospective cohort study identified esophageal and gastric cancer patients during 2008–2016 from the Taiwan Cancer Registry, and obtained medication usage and follow-up information from the National Health Insurance Research Database and Death Registry. Analysis groups were defined as ACEIs/ARBs user or non-user based on the usage of ACEIs/ARBs within the 6 months after cancer diagnosis. The stabilized inverse probability of treatment weighting using propensity scores was applied to balance covariates between study groups. We also used Kaplan-Meier estimates and Cox regression to compare survival outcome and estimate hazard ratios (HRs).ResultsWe identified 14,463 and 21,483 newly-diagnosed esophageal and gastric cancer patients during 2008–2016. ACEIs/ARBs users were associated with lower risk of cancer-specific mortality, although only significantly in gastric cancer (gastric: adjusted HR = 0.87, 95% CI = 0.78–0.97; esophageal: adjusted HR =0.88, 95% CI = 0.76–1.02). A better survival outcome was observed among patients who received higher cumulative defined daily dose of ACEIs/ARBs.ConclusionsWe found that using ACEIs/ARBs after cancer diagnosis were associated with lower risk of mortality. Our results add to the knowledge of the benefit of ACEIs/ARBs against mortality in individuals with esophageal/gastric cancer patients with hypertension.

PFKFB4 promotes angiogenesis via IL-6/STAT5A/P-STAT5 signaling in breast cancer.

Breast cancer has become the most newly-diagnosed cancer and the 5th leading cause of cancer death worldwide. The 5-year survival rate of breast cancer is about 90%. However, the 5-year survival rate drops to <30% when metastasis to distant sites occurs. The blood vessel formation (i.e., angiogenesis) plays a crucial role during the metastatic process. In this study, we investigated the role of PFKFB4 in angiogenesis of breast cancer. Employing in vitro HUVEC tube formation or in vivo orthotopic mouse model, and gene editing or specific small inhibitors strategy, and utilizing qPCR, western blot, ELISA, or immunofluorescent/immunohistochemistry staining methods, we found the following: 1) PFKFB4 upregulates IL-6 expression via NF-κB signaling in breast cancer cells; 2) PFKFB4-induced lactate secretion contributes to NF-κB activation in breast cancer cells; 3) IL-6 elicits angiogenesis via STAT5A/P-STAT5 in HUVEC; 4) 5-MPN (a specific PFKFB4 inhibitor) suppresses angiogenesis in vitro and in vivo. Our findings suggest a potential strategy whereby 5-MPN may lead to an improved therapeutic outcome for breast cancer patients.

Abstract 869: Breast tumor gene expression in the mTOR pathway and clinicopathological characteristics in Black women and White women

Abstract Background: Aberrant activation of the mammalian Target of Rapamycin (mTOR) pathway is implicated in breast carcinogenesis and outcomes. Based on protein expression data, the activation could be heterogeneous by race, body fatness, and tumor clinicopathological characteristics. To understand potential impacts of mTOR pathway signaling in breast cancer, we evaluated the association of race and clinicopathological characteristics with gene expression of select mTOR pathway genes in breast tumors. Methods: Study participants were from the Women's Circle of Health Study (WCHS), complemented with samples from the Roswell Park Pathology Network Shared Resource (PNSR). Tumor tissue blocks were collected from 367 newly-diagnosed breast cancer cases (190 Black and 177 White women). Gene expressions of AKT1, EIF4EBP1, MTOR, RPS6KB2, TSC1 were quantitated using NanoString assays. Generalized linear models were performed to relate gene expression levels with demographic and clinicopathological variables. The regression coefficient (β) was converted to percentage difference. Additionally, we conducted an external validation of mTOR gene expression using data from The Cancer Genome Atlas (TCGA; N=332). Results: Study participants were mostly within the ages of 51 to 65 years old. Black women had lower expression levels of AKT1, MTOR, RPS6KB2 and TSC1 compared to White women. Black race vs White race was significantly associated with lower gene expression of AKT1 (-21.34%, 95% CI = -31.61%, -8.61%) and RPS6KB2 (-12.19%, 95% CI = -19.75%, -3.92%). The racial differences in expression levels of these two genes were consistent across luminal A, luminal B, HER2-enriched, and triple-negative subtypes. Higher tumor grade was associated with higher expression levels of EIF4EBP1 and RPS6KB2, but with lower expression of TSC1. In comparison to luminal A tumors, luminal B tumors had higher expression of RPS6KB2 (17.35%, 95% CI = 4.08%, 32.31%); whereas HER2-enriched (-23.66%, 95% CI= -41.73%, -1.00%) and triple-negative (-22.89%, 95% CI= -40.55%, -1.00%) had lower expression of TSC1. All these associations were unchanged after additionally adjusting for body mass index in a subset. Similarly, results from the TCGA data showed that in comparison to luminal A tumors, luminal B tumors had higher expression of RPS6KB2 (53.73%, 95% CI = 27.12%, 87.76%) whereas HER2-enriched had a lower expression of TSC1 (-26.66%, 95% CI = -43.45%, -4.88%) and triple-negative subtype had a lower expression of TSC1 (-17.30%, 95% CI = -50.68%, -3.05%). Conclusions: Variables such as race and breast cancer subtypes should be considered in studying the mTOR pathway genes in breast cancer tumors. Citation Format: Mmadili N. Ilozumba, Song Yao, Adana A. Llanos, Angela Omilian, Weizhou Zhang, Susmita Datta, Chi-Chen Hong, Warren Davis, Thaer Khoury, Christine B. Ambrosone, Ting-Yuan D. Cheng. Breast tumor gene expression in the mTOR pathway and clinicopathological characteristics in Black women and White women [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 869.

Traditional Chinese Medicine Reduces the Incidence of Chemotherapy-Induced Stroke: A Five-Year Nationwide Population-Based Cohort Study From Taiwan.

Background: Chemotherapy is suspected to be a risk factor for stroke in patients with cancer, athough the results from large-scale studies are controversial. Few strategies are available for reducing the stroke-related risks. Methods: We analyzed stroke incidence rates in Taiwan’s Longitudinal Health Insurance database 2000 (LHID2000) for patients aged ≥20 years with newly-diagnosed cancer between Jan 1, 2000 and Dec 31, 2006, who did or did not receive chemotherapy. Moreover, we compared stroke incidence rates among chemotherapy users who did or did not use traditional Chinese medicine. All study participants were followed-up for 5 years or until they had a stroke. Results: In adjusted Kaplan-Meier analysis, the incidence of stroke was higher within the first year of cancer diagnosis among chemotherapy recipients compared with those who did not receive chemotherapy (31.1 vs. 9.75; adjusted subdistribution hazard ratio [sHR] 2.21; 95% confidence interval [CI], 1.52–3.20; p < 0.001). This between-group difference persisted at 4 years of follow-up (13.6 vs. 5.42; adjusted sHR 1.94; 95% CI, 1.53–2.46; p < 0.001). Similarly, the 5-year incidence rate of stroke was significantly lower among chemotherapy recipients using TCM vs. non-TCM users (0.19 vs. 0.46; adjusted sHR 0.45; 95% CI, 0.26–0.79; p < 0.001), as was the mortality rate (adjusted sHR 0.55; 95% CI, 0.44–0.68; p < 0.001). Conclusion: These Taiwanese data suggest that chemotherapy is a risk factor for stroke and that the use of TCM can significantly mitigate this risk. TCM also appears to reduce the mortality risk associated with chemotherapy.

Dysregulation of soluble immune checkpoint proteins in newly-diagnosed early breast cancer patients.

556 Background: Checkpoint proteins regulate the immune system. Breast cancer (BC) cells exploit the up-regulation or down-regulation of these proteins to evade anti-tumor immune responses. Soluble forms of immune checkpoint molecules (ICM) can be measured in human plasma, however their biological and clinical significance remains essentially unknown. The aim of the present analysis was to measure the pre-treatment ICM in newly- diagnosed BC patients (pts) and compare them to healthy controls. Methods: Soluble forms of ICM, as well as cytokines and chemokines, were measured using Multiplex bead array and ELISA technologies. Plasma samples from 98 BC pts and 45 healthy controls were analyzed for each protein. Data was prospectively obtained. Measured levels were compared between BC pts and healthy controls using a non-parametric test (Mann-Whitney). P-values below 0.05 were considered statistically significant. Results: Soluble stimulatory molecules GITR (p &lt; 0,000002), GITRL (p &lt; 0,007), CD27 (p &lt; 0,002), CD28 (p &lt; 0,003), CD40 (p &lt; 0,003), CD80 (p &lt; 0,009), ICOS (p &lt; 0,0006), as well as inhibitory molecules PD-L1 (p &lt; 0.0000001), CTLA-4 (p &lt; 0,005), TIM-3 (p &lt; 0,00006), HVEM (p &lt; 0,00002) TLR-2 (p &lt; 0,05), levels were significantly lower in early BC pts compared to healthy controls. When analyzed according to BC characteristics (TNBC vs. non-TNBC, tumor size, stage, nodal status and age) no significant difference was detected between the soluble levels of these ICM between the different subsets. Additionally, serum CXCL5 (p &lt; 0,000001), CCL23 (p &lt; 0,04), IL-16 (p &lt; 0,00005), interferon-α (p &lt; 0,03) and IL1-RA (p &lt; 0,03) were significantly lower compared to healthy controls. Serum CX3CL1 or fractalkine (p &lt; 0,024465) was significantly higher compared with healthy controls. Serum interferon-γ (p &lt; 0,2), IL-6 (p &lt; 0.6) and IL-2 (p &lt; 0.6) levels were not significantly different between the BC pts and the healthy controls. Conclusions: We identified low levels of both the stimulatory and inhibitory immune checkpoint molecules, in newly-diagnosed, non-metastatic BC pts compared to healthy controls. These results indicate that early BC is associated with a down-regulation of both soluble stimulatory and inhibitory immune-checkpoint pathways. Newly-diagnosed early BC pts have a generalized immune-suppression independent of subtype (TNBC vs non-TNBC) and stage, which, to our knowledge, is the first study to describe soluble immune checkpoints in early BC pts.

Correlation between Demographic, Socio-economic, and Cancer-specific Factors with Quality of Life Scores among Newly-Diagnosed Cancer Patients of the Medical Oncology Clinics of the Philippine General Hospital Cancer Institute

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Abstract SS1-09: Medicaid expansion associated with earlier stage and improved reconstruction rates in low income breast cancer patients

Abstract Introduction: Substantial delays in time to initiation of treatment (TTT) following diagnosis of breast cancer (BC) can inflict a toll on quality of life and can decrease cancer-specific survival. Among low-income, non-elderly Ohio women having newly-diagnosed breast cancer with local or regional spread, we examined TTT and other measures where income-related disparities have been documented, comparing 2011-2013 (pre-Medicaid-expansion) vs. 2014-2016 (post-expansion). Our primary hypothesis was that TTT would decrease following 2014 Medicaid expansion.Methods: Using data from the Northeast Ohio Cancer Assessment and Surveillance Engine (NEO-CASE), a multilevel data infrastructure linking Ohio cancer registry data with community data, we identified 30-64 year-old women with new diagnosis of invasive, non-metastatic BC who were uninsured or on Medicaid when diagnosed. TTT was defined as days from diagnosis to first BC treatment with any modality. We excluded women with TTT=0 (likely coding error). The main exposure was pre- or post-Medicaid expansion period defined as 2011-2013 or 2014-2016, respectively. We examined additional key demographic and treatment variables before and after expansion and in multivariate analysis of TTT. We used a previously-described probability-weighting approach based on neighborhood median income to approximate excluding women with incomes above 138% of Federal Poverty Level. As a control analysis, we compared pre- and post-expansion TTT among privately insured women, probability weighted to select for higher income individuals.Results: Our study population included 1177 and 1143 women diagnosed with BC pre- and post-expansion, respectively. Demographic characteristics were similar, though mean age increased by 1.2 years (p&amp;lt;0.01) post-expansion. Mean TTT increased by 2 days post-expansion, from 41.1 to 43.1 (p=0.18). The control analysis showed a similar small post-expansion increase. Though no significant change in TTT was observed, the percent uninsured in the low-income group fell by more than half (from 32.9% to 14.1%; p&amp;lt;0.01), and the percent of women diagnosed with regional stage disease decreased from 38.1% to 30.9% (p&amp;lt;0.01). The percent of women undergoing reconstructive surgery increased from 12.1% to 16.7% (p&amp;lt;0.01) from the pre- to the post-Medicaid expansion period, a change not observed in the privately-insured control group. Cox proportional hazards regression models controlling for the effect on TTT of covariates shown in the table revealed an adjusted hazard rate (AHR) of 0.950 (95% CI 0.855 to 1.056) associated with Medicaid expansion. Stage-stratified Cox models showed a similar lack of effect among women with local and regional disease. Discussion: TTT increased by 2 days post-expansion; however, this increase was neither statistically significant nor clinically meaningful. Despite the lack of improvements in TTT, we note the dramatic drop in the percent uninsured among BC patients post-expansion, as well as a marked decrease in the percent of women diagnosed with regional-stage disease, and an increase in BC patients undergoing reconstruction. Taken together, these trends show an overall positive impact of Medicaid expansion on BC process of care and outcome measures. Pre-expansionPost-expansionpN11771143Mean TTT in days (SD)41.1 (37.1)43.1 (33.7)0.18Mean age at diagnosis (SD)51.6 (8.39)52.8 (8.14)&amp;lt;0.01Non-Hispanic African American (%)269 (22.9)225 (19.7)0.07Married/Partnered (%)408 (34.7)417 (36.5)0.38Uninsured (%)387 (32.9)161 (14.1)&amp;lt;0.01Non-metropolitan census tract (%)285 (24.2)232 (20.3)0.03Area Deprivation Index 9 or 10: most deprived (%)274 (23.3)238 (20.8)0.17Regional disease (%)448 (38.1)353 (30.9)&amp;lt;0.01Reconstructive surgery (%)143 (12.1)191 (16.7)&amp;lt;0.01Breast conserving surgery (%)509 (43.2)590 (51.6)&amp;lt;0.01 Citation Format: Johnie Rose, Weichuan Dong, Uriel Kim, Samilia Obeng-Gyasi, Siran Koroukian. Medicaid expansion associated with earlier stage and improved reconstruction rates in low income breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS1-09.