Characterization of Uterine Cervix Cancers in Women from Appalachian Kentucky

Uterine cervix cancer (UCCx) is clinically and socioeconomically diverse among women in the United States (US), which obscures the discovery of effective radiochemotherapy approaches for this disease. UCCx afflicts 7.5 per 100,000 American women nationally but 11.7 per 100,000 women in Appalachian Kentucky (AppKY), when age-adjusted to the 2000 US standard population. Epidemiological chart review was performed on 212 women with UCCx treated at the University of Kentucky (UKY) between January 2001 and July 2021. Demographics, tumor characteristics, and relative radiochemotherapy dose and schedule intensity were compared among AppKY and non-AppKY cohorts as well as Surveillance, Epidemiology, and End Results (SEER) data. One hundred thirty-eight (65%) of 212 women seeking radiochemotherapy treatment for UCCx resided in AppKY. Most (80%) sought external-beam radiochemotherapy close to their AppKY residence. Brachytherapy was then most frequently (96%) conducted at UKY. Cancer stage at diagnosis was significantly more advanced in AppKY residents. Women residing in AppKY had a median 10-week radiochemotherapy course, longer than an 8-week guideline. Estimated survival in women residing in AppKY was 8% lower than US national averages. In summary, this study identified an increased percentage of advanced-stage UCCx cancer at diagnosis arising in AppKY residents, with a confounding population-specific delay in radiochemotherapy schedule intensity lowering survival.

Modeling the age distribution of retinoblastomas

In this work, based on real data on the size of the eyeball (in a fetus, in a child, and in young people under 20), we constructed a model function of the growth of the retinal cell tissue. We used this function to construct a theoretical age distribution of retinoblastomas. We constructed theoretical age distributions for four different models of retinoblastoma: a complex mutational model, a third mutational model, a model with a sequence of key events, and a model of a single oncogenic event with two different latencies (hereditary and non-hereditary retinoblastoma). We compared the theoretical age distribution of retinoblastomas with the real age distribution based on SEER data (Surveillance Epidemiology and End Results; program of the American National Cancer Institute). In total, we examined 843 cases in women and 908 cases in men. For all models (separately for women and men), we obtained estimates of the following cancer parameters: the specific frequency of key events (events that trigger cancer); the duration of the latency period of cancer; the number of key events required for cancer to occur. For the composite age distributions, we calculated the theoretical mean age at diagnosis for hereditary and non-hereditary retinoblastomas. The best approximation accuracy (for male and female forms of retinoblastoma) is shown by a model with a sequence of key events.

Pediatric Acute Lymphoblastic Leukemia: Database Analysis of Patients and Treatments in a National Public Healthcare System

Introduction: Despite the achievement of progressively higher cure rates, acute lymphoblastic leukemia (ALL) remains the main cause of cancer-related deaths in children, adolescents, and young adults, particularly in low- and middle-income countries. According to SEER data, the 3-year survival for ALL ages <20 in 2015 in the US was 90.4%-92.5%. Since new immunotherapy strategies are approved up to the age of 25 years, these young adults should also be included in outcomes analyses. It is important to determine outcomes and the gap between the overall survival observed in developing and in high-income countries to guide policies and priorities regarding specific healthcare needs and, ultimately, to improve the outcomes of ALL treatments worldwide. Objectives: To describe the treatment lines, protocols and fatality rates in children, adolescents and young adults up to the age of 25 years diagnosed with ALL (PedALL) in Brazil, based on a public healthcare national database. Methods: The "DataSUS" is an anonymized open-access database of all patients treated in Brazilian public healthcare centers, divided in three datasets: outpatient, inpatient, and death reports. Citizens have a unique number and all diagnoses, diagnostic procedures and medical interventions are included. This national registry is used to track public expenses. DataSUS has information regarding ALL (ICD-10, C91.0) including protocols, treatment lines, and survival. We performed a descriptive cross-sectional study of PedALL included in the database between Jan/2013 and Dec/2018 to understand the burden of the disease in the public healthcare system. Then, we selected a cohort of patients with PedALL included in DataSUS as "First-line chemotherapy for pediatric leukemia" between Jan/2014 and Dec/2015, and followed these patients until Dec/2018, to describe the management and outcomes of PedALL in our country. Results: Between 2013 and 2018, 17,658 patients ages 0-25 years (86% < 18 years) had the underlying diagnosis of ALL, a mean of 6,045 patients per year: 2,725 newly diagnosed, and the remaining, continuation therapy. The male/female ratio was 1.40. The patients underwent a total of 86,332 procedures in this timeframe including diagnostic procedures, chemotherapy, multiple treatment lines, hematopoietic stem cell transplant, transplant-related exams, and the management of disease and treatment-related complications. Treatment protocols most frequently reported were BFM and two national protocols, GBTLI-LLA and RE-LLA. A total of 1,266 patients died between 2013-2018, a mean of 211 patients each year, 79.3% of them younger than 18 years of age. In the cohort diagnosed between Jan/2014 and Dec/2015, 2,368 patients 0-18 years of age and 91 ages 19-25 years were first included in DataSUS system as "First-line chemotherapy for pediatric leukemia". The male:female ratio was 1.44 and 1.84 for the 0-18 and 19-25 years of age, respectively. The median time from diagnosis to treatment initiation was 2.3 months. Within the three year-follow-up, a 2 nd line chemotherapy was registered in 142 patients (6%), 3 rd line in 11 patients (0.46%) and a 4 th line in a single patient (0.04%). The mean duration of each treatment line was 16.4, 8.3, and 4 months, respectively, for the 1 st, 2 nd, and 3 rd line. Patients were hospitalized for a mean total of 65.3 days: 9.7 admissions per patient, for a mean of 6.7 days each. The absolute death count was 303 (0-18) and 13 (19-25) patients, which would represent a 3-year fatality rate of 12.8% (0-18) to 14.3% (19-25); 61% of the deaths occurred in the first year of treatment. Conclusion: The burden of ALL for the public health care system is large, with over 80 thousand procedures every year. This has a high emotional and socio-economic impact to the families and to the society. More than 200 children and young adults with ALL die every year in Brazil, but fatality rate is very similar to SEER data. The two-month delay between diagnosis and treatment initiation can be an explanation for the early mortality observed in our database and must certainly be appointed as a great opportunity for improvement. Standardization of the national PedALL protocol and new treatment modalities may greatly improve this scenario. Disclosures Queiroz Hazarbassanov: Novartis: Current Employment.

SURG-14. COMPARABLE SURVIVAL OUTCOMES BETWEEN THE ELDERLY AND THEIR YOUNGER COUNTERPARTS AFTER RESECTION OF BENIGN MENINGIOMAS

OBJECTIVE Using the Surveillance, Epidemiology and End Results (SEER) database, we characterized the patterns of surgical recommendations and outcomes after benign meningioma resection in the elderly population. METHODS 27,839 adult meningioma patients were identified in SEER between 1973- 2015 and 6,967 patients were identified between 2016-18. Patients were stratified into four age groups:18-39, 40-59, 60-79, and > 80 years old. The likelihood for recommendation to proceed with resection, extent of resection, and survival outcome were determined using logistic regression models. RESULTS In a multi-variate model that accounted for gender, race, marital status, tumor size, and tumor location, the likelihood of recommendation to proceed with benign meningiomas resection decreased with advancing age. Relative to patients age 40-59, the likelihood of recommendation for surgery were 1.130 (95%CI=0.925-1.380, P=0.230), 0.593 (95%CI=0.531-0.662, P< 0.001), and 0.173 (95%CI=0.146-0.205, P< 0.001) for patients age 18-39, 60-79, and >= 80, respectively. A similar trend in the likelihood of gross total resection (GTR) was observed. Relative to patients age 40-59, the likelihood of gross total resection were 1.009 (95%CI=0.913-1.114, P=0.867), 0.903 (95%CI=0.849-0.961, P=0.001), and 0.580 (95%CI=0.512-0.657, P< 0.001) for patients age 18-39, 60-79, and >= 80, respectively. However, survival after meningioma resection did not vary significantly as a function of patient age. Relative to patients age 40-59, the hazard of death after GTR of meningioma resection were 1.324 (95%CI=0.795-2/203, P=0.280), 0.813 (95%CI=0.639-1.035, P=0.092), and 0.913 (95%CI=0.618-1.350, P=0.649) for patients age 60-79, and >= 80, respectively. These results were validated using SEER data from 2016-2018. CONCLUSION This analysis provide evidence that surgeons exert caution in surgical resection of benign meningioma in the elderly, with decreased likelihood for recommending surgery in this population. In patients selected for and underwent gross resection, survival outcome in the elderly was comparable to their younger counterparts, suggesting safety of procedure in appropriately selected elderly.

Nomogram Predicting Cancer-Specific Death in Parotid Carcinoma: a Competing Risk Analysis

PurposeMultiple factors have been shown to be tied to the prognosis of individuals with parotid cancer (PC); however, there are limited numbers of reliable as well as straightforward tools available for clinical estimation of individualized mortality. Here, a competing risk nomogram was established to assess the risk of cancer-specific deaths (CSD) in individuals with PC.MethodsData of PC patients analyzed in this work were retrieved from the Surveillance, Epidemiology, and End Results (SEER) data repository and the First Affiliated Hospital of Nanchang University (China). Univariate Lasso regression coupled with multivariate Cox assessments were adopted to explore the predictive factors influencing CSD. The cumulative incidence function (CIF) coupled with the Fine-Gray proportional hazards model was employed to determine the risk indicators tied to CSD as per the univariate, as well as multivariate analyses conducted in the R software. Finally, we created and validated a nomogram to forecast the 3- and 5-year CSD likelihood.ResultsOverall, 1,467 PC patients were identified from the SEER data repository, with the 3- and 5-year CSD CIF after diagnosis being 21.4% and 24.1%, respectively. The univariate along with the Lasso regression data revealed that nine independent risk factors were tied to CSD in the test dataset (n = 1,035) retrieved from the SEER data repository. Additionally, multivariate data of Fine-Gray proportional subdistribution hazards model illustrated that N stage, Age, T stage, Histologic, M stage, grade, surgery, and radiation were independent risk factors influencing CSD in an individual with PC in the test dataset (p < 0.05). Based on optimization performed using the Bayesian information criterion (BIC), six variables were incorporated in the prognostic nomogram. In the internal SEER data repository verification dataset (n = 432) and the external medical center verification dataset (n = 473), our nomogram was well calibrated and exhibited considerable estimation efficiency.ConclusionThe competing risk nomogram presented here can be used for assessing cancer-specific mortality in PC patients.

The value of innovation: association between improvements in survival of advanced and metastatic non-small cell lung cancer and targeted and immunotherapy

Background Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns. Methods We utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort. Results We included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time. Conclusion Our findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.