e23029 Background: Underrepresentation of older adults (≥65 years) in clinical trials may limit important evidence for regulatory and clinical decision-making. Prior FDA analysis 1 demonstrated underrepresentation of older adults in oncology clinical trials. With recent efforts to encourage inclusion of older adults, we evaluated representation in clinical trials using updated data. Methods: This analysis used patient-level data from pivotal trials supporting approvals of new drugs and biologics, and expanded indications from 2010-2020 for cancers with high incidence in the U.S. population and older adults: breast (BC), colorectal (CRC), non-small cell lung (NSCLC), prostate (PC), chronic myeloid leukemia (CML), and multiple myeloma (MM). Age distribution of trial participants compared to incident cases from the NCI SEER Program was analyzed using the Enrollment to Incidence Ratio (EIR). For each cancer-age group, EIR is the percentage of trial participants divided by percentage of incident cases. Previously established EIR categories of < 0.8, 0.80-1.20, and > 1.2 indicate under-, adequate, and over-representation, respectively. Results: The analysis included 86000 participants in 152 trials. Adults >65 yrs were underrepresented in BC trials. Adults >75 yrs were underrepresented in BC, CRC, NSCLC, CML, and MM trials (Table 1). Conclusions: Despite slight variation across cancers, adults >75 yrs appeared to be underrepresented in clinical trials, excepting PC. Given heterogeneity in the natural history by cancer site, incidence may not best represent age distribution of the intended use population for all trials. Further evaluation using prevalence as a comparator may provide additional insights. Additionally, results may be affected by clinical factors such as stage; however, comparison is limited by SEER data element availability. Planned sensitivity analyses such as stratification by drug class and line of therapy may further elucidate enrollment patterns. References: Singh H, Kanapuru B, Smith C, et al: FDA analysis of enrollment of older adults in clinical trials for cancer drug registration: A 10-year experience by the U.S. Food and Drug Administration. Journal of Clinical Oncology 35:10009-10009, 2017. [Table: see text]
e18527 Background: Ovarian cancer is the fifth leading cause of cancer mortality among U.S. women. Because clinical trials have historically not been demographically representative of real-world patients, an understanding of the extent of disparities is an important step in addressing them. We aimed to evaluate the representation of older adults and racial and ethnic minorities in trials for ovarian cancer drugs. Methods: We conducted a pooled analysis of all trials that were submitted to the U.S. Food and Drug Administration (FDA) from January 1, 2010 to December 31, 2020 in support of marketing applications for epithelial ovarian, fallopian tube, or primary peritoneal indications. Demographic data (age, race, and ethnicity) for adult participants were analyzed alongside incident ovarian cancer case data (diagnosis between 2010 and 2019) from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. Enrollment to Incidence Ratio (EIR) is reported and defined as the percentage of participants divided by percentage of U.S. incident ovarian cancer cases. An EIR between 0.80-1.20 indicates adequate representation; <0.80 or >1.20 indicates underrepresentation or overrepresentation, respectively. Participants with race or ethnicity categories reported as unknown or missing, or insufficient for calculation were not included in this analysis. A sensitivity analysis was conducted to evaluate the exclusion of trials enrolling only BRCA+ participants. Results: The analysis included 8,211 participants enrolled across 15 clinical trials. Age was available for all participants; race/ethnicity was not reported for 16.3% of participants. With increasing age, EIR decreased (Table). Non-Hispanic (NH) White participants had the highest EIR of all racial/ethnic groups, while NH Black and Hispanic participants had the lowest EIR. Results were similar when excluding trials enrolling only BRCA+ participants. Conclusions: Adults aged ≥75, NH Black, and Hispanic participants were underrepresented in registrational trials for new ovarian cancer therapies. To enhance understanding of the correlation between age, race, and ethnicity, further analyses are necessary. Prospective measures are essential, as discussed in recent FDA guidances, to enroll an adequately representative population in ovarian cancer clinical trials.[Table: see text]
Abstract Introduction: Approximately 25% of women in the United States experience a symptomatic pelvic floor disorder such as urinary incontinence, pelvic organ prolapse, anal incontinence, and sexual dysfunction. Aspects associated with breast cancer treatment such a chemotherapy, oophorectomy/ovarian suppression, and endocrine therapy may predispose women to pelvic floor disorders. The prevalence of pelvic floor disorders among breast cancer survivors has been cited at 18%, but unpublished cross-sectional data suggests the prevalence may be much higher. In this study, 8.5% - 11.5% of participants experienced prolapse symptoms, 56.2% experienced anal incontinence symptoms, and 43.3% - 51.2% experience urinary incontinence symptoms. While pelvic floor dysfunction is associated with lower quality of life, it is unknown if breast cancer survivors with pelvic floor disorders experience decreased quality of life. The primary aim of this study was to assess if breast cancer survivors with pelvic floor disorders experience lower quality of life. Methods: Women 18 years or older who were previously treated for breast cancer and who were enrolled in a cancer research registry were invited to complete the Pelvic Floor Distress Inventory 20 (PFDI-20), the Female Sexual Function Index (FSFI), and the Short Form 12. Demographic and clinical data were abstracted from the research registry. A participant was considered eligible for the study if she had enrolled in the cancer registry and completed all core questions (i.e. demographics, cancer diagnosis, cancer treatment, endocrine therapy, medical/surgical history, and risk factors). As per standard PFDI-20 reporting, presence of a symptom was defined as answering a 1, 2, 3, or 4 to a question, while presence of a bothersome symptom was defined as answering a 2, 3, or 4. A score of 26 or less on the FSFI was considered indicative of sexual dysfunction. Results: A total of 634 women were considered eligible for enrollment in the study. 445 were able to be contacted, and 410 women agreed to participate in the study. Of those, 303 returned the PFDI-20 questionnaire and FSFI questionnaire, and 264 returned the SF-12 for response rates of 74% and 64%, respectively. Overall, higher scores on the PFDI-20 was associated with lower scores on both the physical and mental components of the SF-12 (Rho = -0.298, p = <.0001; Rho = -0.202, p = .0009, respectively). When the PFDI-20 was broken into subscores, higher POPDI scores (prolapse) was associated with lower physical component scores but not lower mental component scores. Higher CRADI scores (anal incontinence) and UDI-6 scores (urinary incontinence) were associated with lower physical and mental scores. Neither overall FSFI scores or subset domain scores were associated with lower physical or mental component scores of the SF-12. In linear regression analysis, PFDI summary score remained statistically significantly related to both mental and physical component subscores after controlling for age, race, stage of breast cancer, time since diagnosis, and use of adjuvant endocrine therapy. FSFI scores were related to age and endocrine therapy use, but were not related to SF-12 scores. Conclusion: Among a subset of breast cancer survivors, pelvic disorders including pelvic organ prolapse, urinary incontinence, and anal incontinence exist, and these disorders are associated with decreased mental wellbeing. All pelvic floor disorders except pelvic organ prolapse were associated with decreased physical wellbeing. None of the domains of female sexual dysfunction were associated with decreased physical or mental wellbeing among breast cancer survivors. A subset of breast cancer survivors experiences bothersome pelvic floor disorders and thus screening for these disorders can increase referrals to appropriate treatment and complement survivorship care to enhance overall quality of life. Citation Format: Jon F Pennycuff, Felice Yang, Tania Lobo, Caroline Jackman, Colleen McGuire, Ami Chitalia, Kristi Graves. Pelvic floor disorders and quality of life among breast cancer survivors [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 PS9-26.
Abstract Background: Lung cancer is frequently diagnosed in older adults. As the U.S. population continues to age, understanding treatment effects in lung cancer patients ≥65 years of age is increasingly important. Despite this trend, clinical trials (CTs) have historically under-enrolled older adults, creating a disparity between trial and real-world populations. Disproportionate enrollment can create challenges in understanding utilization in subpopulations. Due to increased interest in PD-(L)1 inhibitors for non-small cell lung cancer (NSCLC) treatment, CTs examining PD-(L)1 inhibitors in the first-line (1L) setting were selected to evaluate enrollment disparity in NSCLC immunotherapy. Methods: We identified 11 CTs that investigated 1L NSCLC anti-PD-(L)1 regimens submitted to the FDA between 2016 and 2020. Descriptive statistics were calculated based on the pooled dataset and compared with incident U.S. NSCLC cases diagnosed between 2015 and 2019, based on data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. While SEER is a U.S. population-based representative sample, data from the trials included patients outside the U.S. that were submitted to support marketing applications with applicability to U.S. clinical practice. Results: A total of 7,030 patients enrolled in anti-PD-(L)1 CTs were included. In this sample, 48.2% were age ≥65 years, compared to 70.4% of incident U.S. NSCLC cases. This disparity persists with increasing age: 10.3% of enrollees were age ≥75 years and 0.5% of enrollees were age ≥85 years, compared to 34.3% and 7.2% of incident U.S. NSCLC cases, respectively. Discussion: Based on our results, older adults continue to be underrepresented in NSCLC anti-PD-(L)1 CTs, contributing to a potential treatment evidence gap. This gap widens with age and patients age ≥85 years constitute a miniscule portion (0.5%) of the CT cohort. Meanwhile, more patients will move into this group as the population ages. Aging can be associated with comorbidities and the potential for variance in patient and provider treatment preferences, which are important to acknowledge as these aspects may, in part, explain the results. Nonetheless, the gap in the number of older adults enrolled in this CT sample compared with SEER incidence demonstrates a clear need to improve recruitment in this underrepresented population. Awareness of trial-level and system-level barriers is necessary to minimize disparities. Additional research using tools such as real-world data to examine current treatment utilization, patient factors, and outcomes among underrepresented populations would increase the depth of evidence to address this disparity effectively. Citation Format: Felice Yang, Jonathon Vallejo, Oladimeji Akinboro, Catherine Lerro, Pallavi Mishra-Kalyani, Shenghui Tang, Paul G. Kluetz, Harpreet Singh, Donna R. Rivera. Enrollment of older adults in non-small cell lung cancer (NSCLC) clinical trials compared with population-based U.S. incidence [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A024.
This article assumes two stages in the formation of the bones in the calvaria, the first one takes into account the formation of the primary centers of ossification. This step counts on the differentiation from mesenchymal cells into osteoblasts. A molecular mechanism is used based on a system of reaction-diffusion between two antagonistic molecules, which are BMP2 and Noggin. To this effect we used equations whose behavior allows finding Turing patterns that determine the location of the primary centers. In the second step of the model we used a molecule that is expressed by osteoblasts, called Dxl5 and that is expressed from the osteoblasts of each flat bone. This molecule allows bone growth through its borders through cell differentiation adjacent to each bone of the skull. The model has been implemented numerically using the finite element method. The results allow us to observe a good approximation of the formation of flat bones of the membranous skull as well as the formation of fontanelles and sutures.
Abstract Background: Small cell lung cancer (SCLC) is an aggressive form of cancer characterized by rapid progression, early metastases, and poor prognosis. Clinical trials (CTs) leading to approval of various classes of medical products have recently increased the treatment options available for SCLC patients. Older adults ≥65 years of age are historically under-enrolled in CTs. The U.S. population continues to age. There is often limited evidence supporting safety and effectiveness of treatment among this population because of disproportionate enrollment of older adults in CTs. To characterize patterns of SCLC CT enrollment by age, selected SCLC CTs (immunotherapy and cytotoxic agents) were compared to U.S. SCLC incidence data. Methods: We identified six CTs for treatment of SCLC to support marketing applications submitted to the FDA between 2018-2019. Descriptive statistics based on the pooled CT data were calculated and compared with incident U.S. SCLC cases diagnosed between the same period, using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program. While SEER is a U.S. population-based representative sample, data from the trials included patients outside the U.S. that were submitted to support marketing applications with applicability to U.S. clinical practice. Results: A total of 1,642 patients were enrolled in the six included SCLC CTs. In this sample, 42.9% were age ≥65 years, compared to 66.6% of incident U.S. SCLC cases. This disparity persists with increasing age: 8.5% of CT enrollees were age ≥75 years and 1.8% of CT enrollees were age ≥85 years, compared to 27.5% and 4.5% of incident U.S. SCLC cases, respectively. Discussion: Based on these findings, older adults are underrepresented in SCLC CTs, while representing a substantially larger proportion of incident U.S. cases. The number of SCLC patients over 65 years is likely to increase the U.S. population continues to age. Aging presents specific challenges with respect to cancer care due to increased presence of comorbidities and the potential for variance in patient and provider treatment preferences, which might partially explain the results. These results demonstrate an opportunity to evaluate and fix barriers to trial entry for older adults to ensure representative evidence generation that is reflective of the epidemiology of the disease and the real-world population. Citation Format: Felice Yang, Oladimeji Akinboro, Catherine Lerro, Fatima Rizvi, Pallavi Mishra-Kalyani, Paul G. Kluetz, Harpreet Singh, Donna R. Rivera. Enrollment of older adults in small cell lung cancer (SCLC) clinical trials compared with population-based U.S. incidence estimates [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A025.
11026 Background: About 6% and 0.3% of the total United States (US) population identify as Asian or NHPI alone, respectively. The most commonly diagnosed cancers among AA & NHPI in the US are breast, prostate, lung, thyroid, and colorectal. Liver, gastric, and head and neck cancers occur in higher rates in AA & NHPI vs. non-Hispanic White. Enrollment of Asian & NHPI patients in multiregional cancer clinical trials may provide additional data regarding intrinsic and extrinsic factors (e.g., diet, infections, environmental exposures) impacting the etiology of cancer. We investigated enrollment trends of NHPI and Asian (within and outside of US) patients in cancer clinical trials that led to an FDA approval from 2010-2022. Methods: We analyzed data from ~98,000 patients in 171 cancer therapeutic clinical trials that led to FDA approvals for breast, prostate, lung, thyroid, colorectal, liver, gastric, and head and neck cancer indications from 2010-2022. Separate race categories of Asian and Native Hawaiian and other Pacific Islander were used. Results: Descriptive statistics of NHPI and Asians within and outside of US enrollment in breast, prostate, lung, thyroid, colorectal, liver, gastric, and head and neck cancer trials that led to an FDA approval from 2010-2022 are summarized in the table. Enrollment of Asian patients in the US was <1% (except for liver cancer) and NHPI patients was <0.2%. Conclusions: Although cancer is the leading cause of death for AA & NHPI, AA & NHPI are under-represented in cancer clinical trials, especially when data are further disaggregated into enrollment of NHPI and Asians within and outside of the US. Cancer etiology may vary in Asians in the US vs. Asia due to different intrinsic/extrinsic risk factors, underscoring the importance of enrolling more AA & NHPI into clinical trials to expand the evidence supporting drug approvals in the US and to advance health equity through clinical trial diversity. [Table: see text]
Although lung cancer screening (LCS) using low-dose CT is recommended for high-risk individuals, screening adherence remains low. We conducted a randomized trial to compare two methods of providing LCS education to Maryland Tobacco Quitline (MTQ) callers in order to assess whether this setting may serve as a teachable moment for LCS-eligible individuals. MTQ callers (50-80 years, 20+ pack-years, prior LCS ≥12 months) completed the baseline and were randomized to the Print- or Web-based version of ShouldIScreen.com. Participants completed 1- and 4-month follow-up assessments to evaluate intervention engagement and LCS-related outcomes. Participants (Print = 152, Web = 146) were 61.7 (SD = 6.3) years old and reported 63.5 pack-years (SD = 36.0). Most identified as Black (54.2%), female (66.1%), having internet access (78.9%), completing other recommended cancer screenings (86.3%), and that they would undergo LCS if recommended by their provider (91.3%). By 4 months, significantly more Print (75.0%) than Web (61.6%) participants had read the materials (P = .01). Most reported the interventions contained "the right amount" of information (92.6%) and prepared them to talk with their doctor (57.2%). Regarding screening-related outcomes, 42.8% (Print) and 43.8% (Web) had scheduled or completed a low-dose CT scan or a shared decision-making visit (P = .86). In a racially diverse sample of LCS-eligible quitline callers, offering LCS educational materials resulted in high intervention engagement and screening-related appointments. As >20% did not have internet access, providing participants' preferred modality (web/print) may improve intervention engagement and knowledge. Improving LCS awareness represents an important opportunity to increase screening among eligible but unscreened quitline callers.
