Delay In Initiation Of Treatment Research Articles

An unusual cause of significantly elevated blood alpha-fetoprotein levels: a case report and literature review

Alpha-fetoprotein (AFP) serves as a crucial diagnostic marker for primary hepatocellular carcinoma (HCC) and germ cell tumors (GCTs), with rare instances of significantly elevated levels in other diseases. In this study, we present a case of an elderly patient who was diagnosed with AFP-producing gastric cancer (AFPGC) following an elevated AFP result during physical examination. In investigating liver cancer at an early stage, the diagnosis was missed because of failure in detecting the lesion, resulting in delayed treatment initiation. AFPGC is a rare aggressive tumor that demands heightened awareness among clinicians to foster early detection, diagnosis, and treatment for improved prognosis.

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4—2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Abstract PO5-10-02: Neighborhood deprivation index and time to initiation in patients with metastatic breast cancer

Abstract Background Cyclin-dependent kinase 4 and 6 inhibitors (CDKi) are first-line therapy for patients with estrogen-positive (ER+) metastatic breast cancer (MBC). The accessibility, usability, and outcomes according to demographic factors have not been well studied in real world practice. Methods Retrospective review of patients with ER+ MBC prescribed first line CDKi therapy at a large NCI-designated cancer center from January 2015 through December 2022. Patient records were abstracted for outcomes including 1) time from CDKi prescription to drug initiation (TTI), 3) time from CDKi initiation to progression, and 3) time from CDKi initiation to death/or 6/30/2022. Patient variables collected were: patient age (continuous), race (patient self-report – Black, White, Other), partner status (Married, Not married), Insurance type (Medicare, Medicaid, Private); Mean BMI; Number of comorbidities (5 categories). Neighborhood deprivation index (NDI) was determined from the patient’s address with higher scores indicating more deprivation. Descriptive, comparative, and correlational statistics were used. Results A total of 173 patients were included in the analysis. Mean age – 63.1, (SD 12.7, range 24-94); race – White n=157, Black n=16; marital status – Married n=102, Not married n=71; mean NDI – 61.0 (SD 23.7, range 6-100); mean BMI – 28.9 (SD 6.9, range 16-48); number of comorbidities – 0 n=35, 1-2 n= 35, 3-4 n = 55, 5-6 n = 20, 7+ n = 28; insurance type – Medicare n = 115, Medicaid n = 21, Private n = 37. TTI: the median TTI was 14 days. There were no statistically significant differences in TTI based on age, race, NDI, or other demographic variables. Time to progression: in the multivariate model, younger age at diagnosis and Medicaid insurance were associated with shorter time to progression. Overall survival: not married, younger age at diagnosis, and Medicaid insurance were associated with shorter overall survival. Discussion Demographic factors are associated with diverse outcomes of MBC therapy, not attributed to delay in CDKi treatment initiation. Personalization of support during MBC illness according to risk factors for worse outcomes may help to equalize incomes. Citation Format: Sneha Rajendran, Dianxu Ren, Marina Petruzzi, Margaret Rosenzweig. Neighborhood deprivation index and time to initiation in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-10-02.

Abstract PO3-15-04: Oncotype DX Recurrence Score as an Informative Tool to Optimize Neoadjuvant Therapy in HR-positive, HER2-negative Breast Cancers

Abstract Oncotype DX Recurrence Score as an Informative Tool to Optimize Neoadjuvant Therapy in HR-positive, HER2-negative Breast Cancers Background: Neoadjuvant therapy (NAT) in HR+/HER2- breast cancers rarely leads to pathological complete response (pCR) and often doesn’t achieve substantial tumor shrinkage. Therefore, neoadjuvant therapy in HR+/HER2- breast cancers has the most value in the assessment of in vivo treatment response. For this purpose, biomarkers that can predict clinical and pathological response to systemic therapy could help inform treatment. The role of Oncotype DX testing in the management of early-stage HR+/HER2- breast cancer has been widely recognized in the adjuvant setting. However, no large prospective studies evaluating the Oncotype DX test in the neoadjuvant setting have clearly shown its predictive or prognostic utility to date. In this study, we evaluated the effect of the recurrence score (RS) on systemic treatment recommendations and its correlation to NAT response. Methods: Patients with clinically selected T2-T4 and/or clinically node positive HR+/HER2- breast cancer who were referred to BC Cancer Vancouver for consideration of NAT between September 2021 – April 2023 were screened for study eligibility. Suitable candidates who agreed to participate in the study had Oncotype DX testing on core biopsy specimens and Ki-67 testing on the core biopsy and final resection specimen. Clinico-pathological information, treatment regimens, operative details, and clinical, radiologic, and pathological responses were recorded. Results: Of the 66 patients who met eligibility criteria, 40 enrolled in the study comprising the accrual rate of 60.6 %. There were multiple factors that influenced patients and/or Oncologists participation in the study highlighting the low uptake of NAT in HR+/HER2- tumors. Technical feasibility of obtaining Oncotype DX from core biopsy samples was 95% which correlates with our previously reported data on a smaller cohort. The mean turnaround time from patient consent to RS report was 18.5 calendar days. The mean time from the initial consult to the start of NAT was 18.8 calendar days. Amongst all tumors tested, 28 % had RS equal or greater than 26 while only 2 % of participants had a score less than 10. Overall, 32 % of treatment recommendations were changed based on RS. Approximately 31% of patients who were initially recommended to receive neoadjuvant chemotherapy were spared from this treatment based on low RS. Conversely, 23.8% of patients who were recommended to pursue upfront surgery were escalated to chemotherapy due to a high RS. Approximately 88 % of the participants who were treated with neoadjuvant chemotherapy had a favourable clinical response and 38.5% had a complete clinical response. There were no pCR observed amongst patients who completed surgery after neoadjuvant chemotherapy, but half of them were rendered eligible for less surgery (either spared a mastectomy and/or an axillary dissection). Conclusions: Oncotype DX testing changed systemic treatment recommendations in one third of neoadjuvant patients and presents a unique opportunity for personalized medicine. Pre-operative testing thus influenced clinical decision-making, allowing treatment de-escalation and omission of chemotherapy in those with a low RS and conversely an earlier escalation of systemic therapy for those with a high RS. Turnaround time of the Oncotype DX assay on a core biopsy sample was acceptable and did not significantly delay treatment initiation. The benefit of the Oncotype DX assay prior to NAT was valuable for predicting in vivo response although pCR was not observed in any of the patients enrolled. Analyses are ongoing to further correlate RS to neoadjuvant response and to dynamic Ki-67 and MRI changes. Citation Format: Lidiya Luzhna, Stephen Chia, Mehrnoosh Pauls, Nathalie Levasseur. Oncotype DX Recurrence Score as an Informative Tool to Optimize Neoadjuvant Therapy in HR-positive, HER2-negative Breast Cancers [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-04.

Antibody-positive autoimmune encephalitis and paraneoplastic neurological syndrome: A Swedish case series.

This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p=.0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.

Predictive modeling of initiation and delayed mental health contact for depression

BackgroundDepression is prevalent among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) Veterans, yet rates of Veteran mental health care utilization remain modest. The current study examined: factors in electronic health records (EHR) associated with lack of treatment initiation and treatment delay; the accuracy of regression and machine learning models to predict initiation of treatment.MethodsWe obtained data from the VA Corporate Data Warehouse (CDW). EHR data were extracted for 127,423 Veterans who deployed to Iraq/Afghanistan after 9/11 with a positive depression screen and a first depression diagnosis between 2001 and 2021. We also obtained 12-month pre-diagnosis and post-diagnosis patient data. Retrospective cohort analysis was employed to test if predictors can reliably differentiate patients who initiated, delayed, or received no mental health treatment associated with their depression diagnosis.Results108,457 Veterans with depression, initiated depression-related care (55,492 Veterans delayed treatment beyond one month). Those who were male, without VA disability benefits, with a mild depression diagnosis, and had a history of psychotherapy were less likely to initiate treatment. Among those who initiated care, those with single and mild depression episodes at baseline, with either PTSD or who lacked comorbidities were more likely to delay treatment for depression. A history of mental health treatment, of an anxiety disorder, and a positive depression screen were each related to faster treatment initiation. Classification of patients was modest (ROC AUC = 0.59 95%CI = 0.586–0.602; machine learning F-measure = 0.46).ConclusionsHaving VA disability benefits was the strongest predictor of treatment initiation after a depression diagnosis and a history of mental health treatment was the strongest predictor of delayed initiation of treatment. The complexity of the relationship between VA benefits and history of mental health care with treatment initiation after a depression diagnosis is further discussed. Modest classification accuracy with currently known predictors suggests the need to identify additional predictors of successful depression management.

Practical method in the diagnosis of diabetic ketoacidosis: end-tidal carbon dioxide

Objectives: Diabetic ketoacidosis (DKA) poses a life-threatening risk in uncontrolled diabetes. Current diagnostic criteria rely on invasive measures, leading to potential delays in treatment initiation. This study aimed to assess the diagnostic utility of noninvasive end-tidal carbon dioxide (EtCO2) measurements in DKA patients. Methods: A prospective, cross-sectional study was conducted in a tertiary-level Emergency Medicine Clinic from January 2021 to January 2023. Participants included adults with DKA symptoms and those with stable vital signs as controls. EtCO2 levels were measured using a capnograph device. Diagnostic criteria for DKA were blood glucose ≥250 mg/dL, ketonuria, ketonemia, and metabolic acidosis (pH&amp;lt;7.3 or bicarbonate &amp;lt;15 mEq/dL). Statistical analysis was performed using SPSS Statistics. Results: Of 730 participants, 120 had DKA, 410 did not, and 200 served as controls. EtCO2 levels significantly differed between DKA, non-DKA, and control groups (P&amp;lt;0.05). EtCO2 correlated with pH, lactate, base deficit, and bicarbonate (P&amp;lt;0.05). ROC analysis showed an AUC of 0.86 for EtCO2 in diagnosing DKA (P&amp;lt;0.01), with 91.67% sensitivity and 74.39% specificity at a cut-off value 23.7. Conclusion: This study suggests that EtCO2 measurement is a valuable noninvasive tool for diagnosing and assessing the severity of DKA in the emergency department. An EtCO2 threshold of &amp;lt;23.7 could prompt consideration of DKA in patients with elevated blood glucose levels. More extensive multicenter studies are warranted to validate these findings further. EtCO2 measurement could facilitate early DKA diagnosis and improve patient outcomes.

Tigroid Enhancement: A Characteristic Enhancement Pattern of the Cerebellar Hemisphere on MRI With Intracranial Dural Arteriovenous Fistulas.

This study aims to investigate a characteristic cerebellar hemisphere enhancement pattern on magnetic resonance imaging (MRI) that could aid in early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). Pretreatment MR images of 57 patients with intracranial DAVFs between January 1, 2017, and February 28, 2023, were retrospectively analyzed. A total of 128 patients with confirmed alternative cerebellar lesions during the same period were included as a control group. All patients underwent enhanced MRI with a 3.0T scanner. The presence or absence of parallel enhanced linear striations on the surface of the cerebellar lesions was documented. Statistically significant differences were determined by the Fisher exact test. Cerebellar lesions were identified in 4 intracranial DAVF patients (7.0%). All 4 patients were male, with an average age of 64 years (range: 58-76 years). The pretreatment MR images of all 4 DAVF patients with cerebellar lesions demonstrated the characteristic tigroid enhancement pattern. Tortuous flow voids were present in the MR images of 3 of the 4 patients. Tigroid enhancement pattern was not observed in the remaining 53 intracranial DAVF patients and all control patients. The differences in the incidence of the pattern were significant (p=0.01). A characteristic tigroid enhancement pattern of the cerebellar hemisphere on MRI may aid in the early and specific diagnosis of intracranial DAVFs, allowing timely treatment and improving outcomes. The identification of a characteristic tigroid enhancement pattern on MRI for cerebellar hemisphere lesions holds significant promise for clinical practice. This pattern serves as a distinctive marker aiding in the early and specific diagnosis of intracranial dural arteriovenous fistulas (DAVFs). Clinicians can now utilize this innovative finding to expedite diagnostic workflows, enabling timely intervention and management strategies. The incorporation of this novel imaging feature enhances diagnostic accuracy, potentially reducing misdiagnosis rates and preventing delays in treatment initiation. Ultimately, this advancement may lead to improved patient outcomes and quality of care in neurosurgical and neuroradiological practice.

Investigating potential disparities by exploring time to surgical thyroid cancer treatment

(1) Delays in initial treatment have been a frequently used metric for assessing disparities in medicine; however, there has been sparse literature on treatment delays in thyroid cancer. We therefore aimed to assess disparities by investigating the association between race/ethnicity, insurance type, and socioeconomic status and time to surgical treatment of thyroid cancer. (2) A retrospective chart review was conducted to collect demographic and clinical data from 443 surgical thyroid cancer patients at Mount Sinai Hospital in 2018–2019. We investigated the time between thyroid cancer diagnosis and surgery by race/ethnicity, insurance, and income groups. (3) Univariate analysis showed that race/ethnicity, insurance type, and SES alone were not statistically significant predictors of earlier time to treatment (p = 0.766, 0.339, 0.435, respectively). On multivariable linear regression, time between diagnosis and surgical treatment was not significantly different for racial minorities compared to non-Hispanic White patients, patients with Medicare/Medicaid compared to private insurance, and patients with lowest income quartile (<$54,585) compared to those with the highest (≥$116,560). (4) Present study showed no significant delays in treatment for different racial/ethnic, insurance, and income groups.

Radiological Features of Herpetic Encephalitis in Children

BackgroundNonspecific clinical manifestations and unclear radiological features may delay treatment initiation in pediatric patients with Herpes simplex encephalitis (HSE). The aim of this study is to analyze the clinical and radiological features of the disease. MethodsClinical, laboratory, and magnetic resonance imaging (MRI) data were obtained retrospectively from a group of 37 hospitalized pediatric patients older than two months and with a polymerase chain reaction-confirmed HSE diagnosis. Clinical severity (i.e., mechanical ventilatory support) and outcome at discharge (i.e., pediatric modified Rankin Scale [ped-mRS]) were also assessed. ResultsMedian age was 14 months (interquartile range: 10-36). All patients survived, 15 (41%) had complete recovery (i.e., ped-mRS = 0), and 10 (27%) had significant residual disability at discharge (i.e., ped-mRS ≥3). Brain MRI was obtained in 31 patients. T2-hyperintense lesions were usually bilateral (28, 90%) and multifocal (30, 97%). Hemorrhage and mass effect were observed in 13 (42%) and 15 (48%) patients, respectively. Parenchymal lesions involved the temporal lobes (94%), insula (90%), parietal lobes (84%), and frontal lobes (61%). Occipital lesions were rare. In multivariable binary logistic regression models the presence of altered consciousness was associated with mechanical ventilation (odds ratio [OR] = 8.2, Nagelkerke R2 = 0.22), whereas the involvement of the occipital lobes (OR = 7.8) and the administration of vasopressors (OR = 12.1) were independent predictors of poor outcome (Nagelkerke R2 = 0.41). ConclusionsBrain MRI is useful for diagnosis and outcome assessment in pediatric HSE. Radiological patterns with common frontotemporal involvement overlap adults, but multifocal and parietal lobe abnormalities are observed as well.

Epidemiology of Spinal Muscular Atrophy Based on the Results of a Large-Scale Pilot Project on 202,908 Newborns

BackgroundThis study presents the findings of a newborn screening (NBS) pilot project for spinal muscular atrophy (SMA) 5q in multiple regions across Russia for a period of 2022 year. The aim was to assess the feasibility and reproducibility of NBS for SMA5q in diverse populations and estimate the real prevalence of SMA5q in Russia as well as the distribution of patients with different number of SMN2 copies. MethodsThe pilot project of NBS here was based on data, involving the analysis of 202,908 newborns. SMA screening assay was performed using a commercially available real-time PCR kit, the Eonis SCID-SMA. ResultsIn one year, 202,908 newborns were screened, identifying 26 infants with homozygous deletion of SMN1 exon 7, yielding an estimated SMA5q incidence of 1:7804 newborns. 38.46% had two SMN2 copies, 42.31% had three copies, 15.38% had four copies, and 3.85% had five copies SMN2. Immediate treatment was proposed for patients with two or three SMN2 copies. Infants with four or more SMN2 copies warranted further investigation on management and treatment. Short-term monitoring after gene therapy showed motor function improvements. Delays in treatment initiation were observed, including the testing for AAV9 antibodies and non-medical factors. ConclusionsThe study emphasizes the need for a standardized algorithm for early diagnosis and management through NBS to benefit affected families. Overall, the NBS program for SMA5q in Russia demonstrated the potential to improve outcomes and transform SMA from a devastating disease to a chronic condition with evolving medical requirements.

Total Laboratory Automation in Clinical Microbiology: A Note on Needs, Challenges, and Applications in a Pandemic Scenario

Recently, an increasing number of publications on automation in diagnostic laboratories, especially in microbiology, has illustrated its potential impact on modern medicine by enhancing the overall quality of culture-based microbiology testing. In the context of clinical microbiology, total laboratory automation (TLA) is now defined as automating the testing workflow, which comprises all phases from sample inoculation to outcome analysis. Hence, there is a need to design or implement proper laboratory automation management processes to enhance workflow, reduce analysis time, and deliver high-quality results without delay in treatment initiation. This review-cum-perspective article highlights the need and current advancements in diagnostic microbiology automation that could revolutionize laboratory operations in healthcare settings. Automation of the workflow is a crucial advancement in the recent history of laboratory diagnostics that unites many diagnostic specializations into a single track to increase the effectiveness, administration, standardization, reliability, and safety of lab tests. While clinical chemistry laboratories adopted and deployed laboratory automation decades earlier, the process of implementing them into routine clinical microbiological practices has several bottlenecks and is still a lengthy process and fraught with technical and regulatory challenges. Moreover, due to outbreaks including the COVID-19 pandemic of recent times, testing volumes are increasing, and automation could probably be a great solution for small and mid-sized laboratories. This article lists the TLA remedies and the specimen-processing tools that are presently available. The need and challenges to implementing automation in microbiological laboratories are discussed with a note on applications in pandemic scenarios.

Time to Diagnosis and Treatment Initiation During the COVID-19 Pandemic Among Rural Patients With Cancer.

Time to diagnosis (TTD) and treatment initiation (TTI) are important measures of access to and quality of cancer care. This study addresses the knowledge gap on the impact of the COVID-19 pandemic on TTD and TTI for rural cancer patients. Sixty-three cancer patients residing in rural areas of the state of Hawaii were surveyed in 2020 to 2021. Overall, 67.5% of participants reported TTD within one month of reporting symptoms to a health care provider. Mean TTI for the overall sample was 55.3 days, and among breast cancer patients, 57.9 days. Compared with pre-pandemic state registry data, mean TTI for the overall sample and breast cancer patients were significantly longer than the state registry null value of 40 days (P = .02 and P =.05, respectively). During the COVID-19 pandemic, cancer patients in rural Hawaii experienced substantial delays in TTI compared with pre-pandemic years.

Impact of the Coronavirus Disease 2019 pandemic on neoadjuvant chemotherapy use in patients diagnosed with epithelial type ovarian cancer.

The Coronavirus Disease 2019 (COVID-19) pandemic posed critical challenges in providing care to ovarian cancer (OC) patients, including delays in OC diagnosis and treatment initiation. To accommodate for delays in OC surgery, the Society of Gynecologic Oncology (SGO) recommended preferential use of neoadjuvant chemotherapy during the pandemic. The purpose of this study was to assess the association of the COVID-19 pandemic with neoadjuvant chemotherapy use in patients diagnosed with OC. This retrospective cohort study included patients diagnosed with stage II-IV ovarian cancer of epithelial subtype between 01/01/2017-06/30/2021 at Kaiser Permanente Southern California (KPSC), a large integrated healthcare system in the United States. Ovarian cancer patients diagnosed between 2017-2020 were identified from KPSC's Surveillance, Epidemiology, and End Results (SEER)-affiliated cancer registry. Patients diagnosed in 2021 were identified from the electronic medical records (EMR) using ICD-10 diagnosis codes, followed by medical chart review to validate diagnosis and extract information on histology and stage at diagnosis. March 4, 2020 was used as the cut-off to define pre-pandemic and pandemic periods. Patients diagnosed with COVID-19 between OC diagnosis and treatment completion were excluded. Data on neoadjuvant chemotherapy use were extracted from the cancer registry and EMR, supplemented by chart review. Modified Poisson regression was used to evaluate the association of the pandemic with neoadjuvant chemotherapy use. Of 566 OC patients, 160 (28.3%) were diagnosed in the pandemic period. Patients diagnosed in the pandemic period were slightly younger (mean age 62.7 vs 64.9 years, p=0.07) and had a higher burden of Charlson comorbidities (p=0.05) than patients diagnosed in pre-pandemic period. No differences in time to treatment initiation were observed by pandemic periods. Neoadjuvant chemotherapy use was documented in 58.7% patients during the pandemic period compared to 47.3% in pre-pandemic period (p=0.01). After adjusting for covariates, patients diagnosed in the pandemic period were 29% more likely to receive neoadjuvant chemotherapy than patients diagnosed in pre-pandemic period [RR(95%CI): 1.29(1.12-1.49)]. Ovarian cancer patients diagnosed in the COVID-19 pandemic were more likely to receive neoadjuvant chemotherapy than patients diagnosed before the pandemic. Future research on patient outcomes and trends in the post-pandemic period are warranted.

Abstract 2237: Determinants of time to cancer treatment initiation at a comprehensive cancer center

Abstract Background: Delays in treatment initiation adversely impact cancer mortality and survival. To inform potential enhancements and targets for our existing oncology patient navigation program, we examined characteristics associated with timely treatment initiation among patients at a tertiary comprehensive cancer center that serves four diverse counties in Southern California. Methods: We performed a retrospective analysis of patients newly diagnosed with non-hematological cancers between January 2020 and June 2023. Using electronic medical record data, we used a multivariable Cox proportional model to examine the association between patient demographic and clinical characteristics and time to treatment initiation (time between first encounter and start of definitive treatment) within a clinical benchmark of 3 months. A hazard ratio (HR)&amp;gt;1 indicates shorter (faster) time to treatment initiation while a HR&amp;lt;1 indicates a longer (slower) time. Results: Our sample included 9,148 patients, who were predominantly &amp;lt;65 years (57%), female (61%), married or with a partner (64%), and retired or unemployed (56%); 50% were non-White. In multivariable analyses, patient’s age, primary language, employment status, cancer diagnosis type, and first treatment type were significant determinants of time to treatment initiation. Faster treatment initiation was observed among patients ages &amp;gt;=75 vs &amp;lt;65 years (HR=1.36, 95% CI 1.23 - 1.52). Among the primary languages spoken in our sample (Spanish, Chinese, Korean, Vietnamese, among others), patients who spoke Armenian vs English also had shorter time to treatment (HR=1.64, 95% CI 1.32 - 2.04). By contrast, longer time to treatment initiation was associated with patients who were retired or disabled vs employed full-time (HR=0.85, 95% CI 0.78 - 0.94, and HR=0.70, 95% CI 0.59 - 0.83, respectively) and underwent radiation or oral chemotherapy vs chemo-infusion (HR=0.65, 95% CI 0.57 - 0.74, and HR=0.82, 95% CI 0.76 - 0.89, respectively). With the exception of melanoma, all diagnoses had a longer time to treatment compared with neuro-oncology. In our multivariable model, sex, marital status, race and ethnicity, and receipt of at least one navigation encounter were not significant determinants. Conclusions: In our study, which overlapped the early stages of the COVID-19 pandemic, findings highlight opportunities to enhance navigation delivery, especially for certain subpopulations, diagnoses, and treatment types with complex scheduling and coordination needs. Future research will explore navigation intensity and other process and clinical outcomes modifiable through navigation. Citation Format: Narissa J. Nonzee, Marianne Razavi, William Dale, Lauren Cai, Annette Mercurio, Lorena Gaytan, Deborah Lefkowitz, Chrissy Kim, Terry Hernandez, Steven Morales, Danilo Duque, Ana I. Tergas. Determinants of time to cancer treatment initiation at a comprehensive cancer center [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2237.

Abstract 4793: Effects of treatment delays on lung cancer survival

Abstract Background: Previous studies have established a link between treatment initiation delays and reduced overall survival in individuals diagnosed with lung cancer. These delays are often influenced by diagnostic complexities, logistical hurdles, and patient-related factors. However, the association between treatment delays and survival outcomes has yet to be extensively investigated using data from a large national cohort. This study aims to fill this research gap and provide unique insights into the relationship between treatment delays and lung cancer survival by utilizing data from a substantial national cohort. Methods: The study population consisted of 3,723 lung cancer patients participating in the NCI PLCO Cancer Screening Trial. Cox Proportional Hazards (PH) Regression analyses examined the time between cancer diagnosis and treatment initiation using several measures including intervals from tumor doubling/stage progression time models by Spratt et al. (1964) and Detterbeck et al. (2008). Analyses controlled for patient and clinical characteristics including age, sex, race/ethnicity, smoking status, histopathologic type, cancer stage, and treatment modality. Data analysis was conducted using Microsoft Excel, STATA, and IBM SPSS software. Results: PH Regression analyses demonstrated a clear association between longer time intervals from diagnosis to treatment initiation and increased risk of mortality. Patients with time intervals exceeding 20 days exhibited a hazard ratio (HR) for mortality of 1.21 (p &amp;lt; 0.001, 95% confidence interval [CI] 1.1158-1.3176). The Spratt tumor progression model, considering intervals exceeding 88 days, revealed a HR of 1.22 (p = 0.03, 95% CI 1.0146-1.4885). On the other hand, the Detterbeck model, which considered intervals exceeding 118 days, did not show a statistically significant association with increased mortality risk. Furthermore, PH analysis identified cigarette smoking status, marital status, and tumor grade as significant predictors of mortality risk. Conclusions: Data from a large national cohort study indicate that delays in lung cancer treatment initiation have detrimental impacts on survival. Treatment initiation shortly after diagnosis had the most significant differential impact on mortality risk. Timely initiation of treatment is of utmost importance and should be prioritized in lung cancer care. By addressing factors contributing to treatment delays, it is likely possible to improve the survival rates of patients with lung cancer. Citation Format: Percy Guzman Montero, Sharon Segura Cordero. Effects of treatment delays on lung cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4793.

Delays to treatment initiation and emergence of drug resistance among new adult tuberculosis patients in Tigray, Northern Ethiopia.

Introduction. Studies in Ethiopia have indicated that tuberculosis (TB) patient's elapsed a long time before initiating treatment.Gap Statement. However, there is very limited evidence on the association of treatment initiation delay with drug resistance.Research Aim. To investigate the association of delayed treatment initiation with drug resistance among newly diagnosed TB patients in Tigray, Ethiopia.Methods. We conducted a follow-up study from October 2018 to June 2020 by recruiting 875 pulmonary tuberculosis (PTB) patients from 21 randomly selected health facilities. Delays to initiate treatment and drug resistance were collected using a standardized questionnaire and standard laboratory investigation. The association of delay to initiate treatment with acquired drug resistance was modelled using penalized maximum-likelihood (PML) regression models. Data were analysed using stata software version 15. Statistical significance was reported whenever the P-value was less than 0.05.Result. The median total delay to treatment initiation was 62 days with an inter-quartile range of 16-221 days. A unit change in time to initiate treatment reduced the risk of acquired drug resistance by 3 %. Being smear-positive at the end of treatment and after 2 months of treatment initiation were significantly associated with a higher risk of acquired drug resistance. Whereas, having a mild clinical condition was associated with a lower risk of drug resistance.Conclusion. Time to treatment initiation delay is associated with an increased risk of the emergence of drug resistance. Efforts targeted towards reducing the negative effects of PTB should focus on reducing the length of delay to initiate treatment.

Multicenter evaluation of an automated, multiplex, RNA-based molecular assay for detection of ALK, ROS1, RET fusions and MET exon 14 skipping in NSCLC.

The current study assessed the performance of the fully automated RT-PCR-based Idylla™ GeneFusion Assay, which simultaneously covers the advanced non-small cell lung carcinoma (aNSCLC) actionable ALK, ROS1, RET, and MET exon 14 rearrangements, in a routine clinical setting involving 12 European clinical centers. The Idylla™ GeneFusion Assay detects fusions using fusion-specific as well as expression imbalance detection, the latter enabling detection of uncommon fusions not covered by fusion-specific assays. In total, 326 archival aNSCLC formalin-fixed paraffin-embedded (FFPE) samples were included of which 44% were resected specimen, 46% tissue biopsies, and 9% cytological specimen. With a total of 179 biomarker-positive cases (i.e., 85 ALK, 33 ROS1, 20 RET fusions and 41 MET exon 14 skipping), this is one of the largest fusion-positive datasets ever tested. The results of the Idylla™ GeneFusion Assay were compared with earlier results of routine reference technologies including fluorescence in situ hybridization, immunohistochemistry, reverse-transcription polymerase chain reaction, and next-generation sequencing, establishing a high sensitivity/specificity of 96.1%/99.6% for ALK, 96.7%/99.0% for ROS1, 100%/99.3% for RET fusion, and 92.5%/99.6% for MET exon 14 skipping, and a low failure rate (0.9%). The Idylla™ GeneFusion Assay was found to be a reliable, sensitive, and specific tool for routine detection of ALK, ROS1, RET fusions and MET exon 14 skipping. Given its short turnaround time of about 3 h, it is a time-efficient upfront screening tool in FFPE samples, supporting rapid clinical decision making. Moreover, expression-imbalance-based detection of potentially novel fusions may be easily verified with other routine technologies without delaying treatment initiation.

Delays in Cervical Cancer Treatment Initiation for Patients Living With or Without HIV in Botswana: An Observational Cohort Analysis (2015-2019)

PURPOSEPresent delays in treatment initiation of chemoradiation or radiation alone for patients with advanced stage cervical cancer in Botswana. METHODSWomen with locally advanced cervical cancer (stages IB2-IVB) were prospectively enrolled in an observational cohort study in 2015-2019. We evaluated delays at 30, 60, 90, 120, 150, and 180 or greater days between the date of diagnosis and treatment initiation. Factors associated with overall survival (OS) were modeled with multivariable Cox proportional hazards regression (aHR). Associations between delays in cervical cancer treatment initiation were evaluated via univariable logistic regression. RESULTSAmong the 556 patients included (median age = 47.9 years), 386 (69.4%) were women living with HIV with a median CD4 count of 448.0 cells/μL (IQR, 283.0-647.5 cells/μL) at diagnosis. Most patients had stages II (38.1%) and III (34.5%) cervical cancer. Early-stage patients experienced longer delays in treatment initiation compared to late-stage patients (p=0.033). Early-stage patients with delays ≥90 days and pathology diagnosis between 2016-2019 (aHR 0.34, p<0.001) versus <90 days decreased the risk of mortality, while those with delays ≥90 days and pathology diagnosis before 2016 (aHR 5.67, p=0.022) versus <90 days increased the risk the mortality. Late-stage patients with delays ≥120 days and pathology diagnosis between 2018-2019 (aHR 1.98, p=0.025) versus <120 days increased the risk the mortality. Early-stage patients with pathology diagnosis between 2016-2019 (OR 2.32, p=0.043) versus before 2016 were more likely to experience delays ≥90 days and late-stage patients who traveled >100 km to the treatment facility (OR 2.83, p<0.001) versus <100 km were more likely to experience delays ≥120 days. CONCLUSIONSDelays in care are common in Botswana, particularly for those living farther from the treatment clinic and at advanced stages. This paper is among the first to show an association between treatment delays and worsened OS at advanced stages of cervical cancer, highlighting the need for interventions to help patients receive timely care in global settings.

Experience with cascade screening: A comprehensive family pedigree analysis of two index patients with Fabry disease.

The wide range of clinical symptoms observed in patients with Fabry disease (FD) often leads to delays in diagnosis and initiation of treatment. Delayed initiation of therapy may result in end-organ damage, such as chronic renal failure, hypertrophic cardiomyopathy, and stroke. Although some tools are available to identify undiagnosed patients, new comprehensive screening methods are needed. In this study, the outcomes of the cascade screening applied to three index cases with FD from 2 familes were investigated. In the pedigree analysis, 280 individuals were included; out of them, 131 individuals underwent genetic testing and cascade screening for FD. During the screening program, a total of 45 individuals were diagnosed, with a diagnostic ratio of 1:15. The average age at diagnosis for all individuals was 30.9 ± 17.7 years, and %25 were pediatric cases (mean age 9.5 ± 5.9 years). Thirty affected relatives were diagnosed from thetwo index cases in Family 1 and 15 individuals were diagnosedfrom one index case in Family 2. There were 13 consanguineous marriages observed among 2 pedigres, in two both spouses were affected, leading to two homozygous affected daughters in one couple. In regions where there is a high prevalence of consanguineous marriages, implementing the cascade screening approach to identify all individuals at risk can be beneficial for patients with FD, specifically women and children.