Initial Cancer Diagnosis Research Articles

Psychosocial impact at diagnosis and coping strategies among women with breast cancer-A qualitative study

BackgroundBreast cancer diagnosis can be devastating and challenging for most women. After the initial shock, they adhere towards adopting multiple strategies that enables them to cope with the situation which directly impacts their day-to-day life. This study seeks to understand the psychological and social impact of diagnosis as well as the coping strategies taken up by these women. MethodsThe study uses a phenomenological approach to examine the lives of newly diagnosed women. Semi-structured interviews were conducted with 12 diagnosed women. These interviews were recorded for clarity as well as future reference. Audio recordings were transcribed verbatim in the local languages and then translated into English. Data was analysed according to steps described in Interpretative Phenomenological Analysis. MAXQDA software was used for coding. ResultsThree prominent themes and eight subthemes emerged after data analysis. Stress and uncertainty, financial distress, family distress, and social withdrawal were the initial psychological effects at diagnosis. Family support and religious belief were the main coping strategies identified. Being unaware of signs and symptoms and misdiagnosis were the reasons behind delay in diagnosis. ConclusionBreast cancer diagnosis impacts the patient's psychological, social, and financial well-being. This consequently burdens not only the patient, but their immediate family as well. This necessitates women to develop different strategies to cope with the situation. Understanding the intricacies of initial breast cancer diagnosis from the perspective of a patient may aid medical professionals in providing holistic cancer therapy.

Retrospective review of patients with lung cancer presenting emergently

BackgroundA significant proportion of lung cancer patients receive their diagnosis as part of an emergency presentation (EPs) to emergency departments (EDs). ObjectivesThis study aimed to describe EPs of lung cancer at a safety-net hospital system. MethodsWe conducted a retrospective analysis of patients with lung cancer at a safety-net ED. EP was defined as a diagnosis of lung cancer due to an acute presentation with symptoms of undiagnosed lung cancer (e.g., cough, hemoptysis, shortness of breath). Non-EPs were the result of either incidental findings (trauma pan-scan) or as part of lung cancer screening. ResultsA total of 333 patient charts were reviewed who had lung cancer. Of those, 248 (74.5%) were defined as having an EP. EPs were more likely stage IV than non-EPs (50.4% vs 32.9%). The percent mortality was higher for EP versus non-EP, 60.0% vs 49.4%. which is driven by a high mortality rate for stage IV EPs (77.5%). Most patients with an EP were seen in the ED (177, 71.4%) as the location of initial visit that had a workup concerning for lung cancer. Most of the EPs were admitted for completion of either their diagnostic work up and/or for symptom management (117, 66.5%). Logistic regression identified significant predictors for an EP including stage IV at diagnosis (OR 2.49, 95% CI 1.39–4.48) and lack of primary care (OR 0.07, 95% CI 0.009–0.53). ConclusionMost patients with lung cancer present acutely as an EP with advanced stage in a safety-net health care setting. The ED plays an important role in the initial diagnosis of lung cancer and coordinating subsequent cancer care.

Study of practice patterns in NGS vs single gene testing, provider-identified barriers to biomarker testing and utilization of liquid biopsy across multiple hospital-based cancer centers.

e18743 Background: Limited data exists on next-generation sequencing (NGS) testing rates, utilization of single gene tests for therapy matching, use of liquid biopsies in therapy selection, or physician-perceived barriers to testing in hospital-based cancer centers. Initial project goal is to establish a baseline for such metrics. Methods: 700 patient records of various solid tumor types were assessed as part of a quality improvement project at three different cancer centers over a six-month period: 1) a regional IDN, 2) an NCI center, and 3) a community cancer center/affiliate of an NCI center. This was combined with qualitative surveys on current state practices and barriers to NGS testing completed by thirty (30) respondents from these institutions (97% physicians, 3% nonphysicians). Site specific Physician champions were recruited to identify additional interventions to be implemented at their respective site(s). Results: Baseline findings show 45% of advanced cancers received any biomarker tissue testing, with testing rates of 53%, 25%, and 66% in lung, pancreas, and colon cancers, respectively. Broad-based panel testing made up 59% of tests, and 31% of patients continue to receive single gene testing only. Approximately one third of patients who developed recurrent disease had biomarker testing (38%) compared to patients with an initial diagnosis of advanced cancer where more than half received testing (51%). Use of liquid biopsies was limited, representing 4% of biomarker testing, but 71% of the time it was incremental to completed tissue testing. Three types of testing barriers were identified by survey respondents: 1) 63% cited limited quantity of tissue available, 2) 53% cited reimbursement concerns including “potential cost to patient,” and 3) 44% cited cumbersome process due to delays and long turnaround times for authorization, ordering, and/or delivery of results. Conclusions: 1) A lower number of patients with disease recurrence are obtaining broad panel NGS compared to patients with de novo metastatic disease; 2) There continues to be low utilization of liquid biopsies for patients with advanced cancers; and 3) Single gene tests continue to be used for therapy matching in a large number of patients with advanced cancers. Improving testing rates including use of broad panel tests and liquid biopsies appropriately will require ongoing education and/or automated reminders to cancer care teams. Further education needs to focus on reimbursement concerns at an institutional level and on testing patients who recur after initial cancer diagnosis and therapy.

Demographic and clinical factors associated with cardiovascular events in elderly long-term survivors of breast cancer.

e24105 Background: Improvements in cancer-specific survival have led to a growing appreciation for non-cancer drivers of mortality, particularly cardiovascular disease (CVD), in long-term cancer survivors. However, studies of population-level, non-oncologic outcomes in long-term survivors as a function of treatment exposures remain limited. Our aim is to evaluate the risk of developing cardiovascular disease (CVD) based on demographic and clinical characteristics in long-term breast cancer survivors, defined as those alive five years after diagnosis. Methods: We conducted a SEER-Medicare retrospective study of patients over age 65 with non-metastatic breast cancer, treated with curative intent surgery, diagnosed between 2003-2011, and enrolled in fee-for-service Medicare. CVD events were defined by the presence of any claims corresponding to stroke, heart failure, myocardial infarction, or cardiomyopathy beginning at 5 years after initial diagnosis and extending through year 10. Chi-squared tests were used to examine associations between demographic and clinical characteristics and CVD status. LASSO regularization was used for variable selection in a cox-proportional hazards model using 10-fold cross validation showing CVD hazard ratios stratified by diagnosis year. Results: 43,347 patients met inclusion criteria, of which 5,444 had a diagnosis of CVD between five years after diagnosis and last follow-up. Compared to patients without evidence of CVD, patients experiencing CVD were more likely to be older, Black, live in impoverished neighborhoods, have stage III (vs. I or II) disease, and have been diagnosed during the latter part of the study period (2009-2011 vs. 2003-2008). Variables included in the model following the LASSO regularization process were age at diagnosis, race/ethnicity, % with poverty, metropolitan residence, cancer stage at diagnosis, receipt of radiation therapy, and diagnosis year. Age, race/ethnicity, and cancer stage at diagnosis were significant predictors of developing CVD during years 5-10 after an initial cancer diagnosis (P < 0.001). Risk of developing CVD increased with age and was associated with a threefold higher risk in women over age 85. Non-Hispanic Black patients were at the highest risk across race/ethnicity groups (HR: 1.48, 95% CI: 1.34 – 1.65), and patients with a stage III diagnosis were at the highest risk by stage (ref Stage I; HR: 1.56, 95% CI: 1.41 - 1.72). Those diagnosed in 2009-2011 were at higher risk of developing CVD than in earlier years (ref 2003-2005; HR: 1.67, 95% CI: 1.56 – 1.79). Conclusions: Age, race, poverty, and cancer stage at diagnosis were associated with increased risk of developing CVD in long-term breast cancer survivors. Patients with elevated non-oncologic risks may benefit from increased participation by primary care as a component of effective cancer survivorship.

Larotrectinib (laro) long-term efficacy and safety in patients (pts) with tropomyosin receptor kinase (TRK) fusion thyroid carcinoma (TC).

6091 Background: Neurotrophic tyrosine receptor kinase ( NTRK) gene fusions are oncogenic drivers in a variety of tumor types, including TC. Laro is a first-in-class, highly selective, central nervous system (CNS)-active TRK inhibitor approved for tumor-agnostic use in pts with TRK fusion cancer based on a rapid, robust, and durable objective response rate (ORR) in both adult and pediatric pts with various cancers. Here, we report data on the subset of pts with TRK fusion TC treated with larotrectinib with long-term follow-up. Methods: Pts with TRK fusion TC enrolled in three laro clinical trials (NCT02576431, NCT02122913, NCT02637687) were included. Laro was administered at 100 mg twice daily to most pts; two pediatric pts received 100 mg/m2. Responses were assessed per independent review committee (IRC) using RECIST v1.1. Data cut-off: July 20, 2022. Results: As of data cut-off, 30 pts were eligible for efficacy assessment by IRC. The median age was 61.5 years (range 6–80) and the median time since initial cancer diagnosis was 5.0 years (range 0–46). The gene fusions involved NTRK1 (n =14; 47%) or NTRK3 (n =16; 53%). Fifteen pts (50%) received no prior systemic therapies, and six (20%) received ≥2; 23 (77%) received prior radioiodine. ORR was 63% (95% confidence interval [CI] 44–80): three (10%) complete response, 16 (53%) partial response (PR), five (17%) stable disease, four (13%) progressive disease, and two (7%) not evaluable. For pts classified as differentiated TC (DTC; n = 23), the ORR was 78% (95% CI 56–93). For pts classified as anaplastic TC (ATC; n = 7), the ORR was 14% (95% CI 0–58). All four pts with CNS metastases at baseline had a PR. Median time to response was 1.9 months, and median duration of response (DoR) was 43.3 months (95% CI 21.6–not estimable [NE]) at a median follow-up of 32.3 months. Median progression-free survival was 35.5 months (95% CI 23.4–NE) at a median follow-up of 34.0 months. Median overall survival (OS) was not reached (NR; 95% CI 48.7–NE) at a median follow-up of 46.4 months; the 48-month OS rate was 71% (95% CI 54–88). Median OS was NR (95% CI 48.7–NE) in DTC and 8.8 months (95% CI 2.6–NE) in ATC. At data cut-off, five pts who had disease progression continued treatment for ≥4 weeks due to continued clinical benefit. Treatment-related adverse events (TRAEs) were predominantly Grade 1–2. Grade ≥3 TRAEs were reported in two (7%) pts (anemia and decreased lymphocyte count). There were no treatment discontinuations due to TRAEs. Conclusions: Laro continues to demonstrate a rapid and durable response, extended survival, and a favorable safety profile in pts with TRK fusion DTC. Limited single-agent activity was observed in ATC. These results support the wider adoption of next generation sequencing panels, which include NTRK gene fusions, in pts with advanced TC prior to the initiation of any systemic therapy. Clinical trial information: NCT02576431 , NCT02122913 , NCT02637687 .

Impact of a pathologist-driven molecular testing protocol on veterans with non-small cell lung cancer.

e21209 Background: Precision medicine has shifted the paradigm of cancer treatment in the last two decades. Currently, with over ten targetable mutations in non-small cell lung cancer (NSCLC) and increasingly emerging biomarkers for immunotherapy, genomic testing is necessary for every NSCLC patient. However, this multiple biomarker-defined treatment approach is often compromised by many challenges including slow turnaround time (TAT), high rate of quantity not sufficient (QNS) resulting in inaccurate molecular testing or needs for second biopsy. These barriers lead to increased risk of developing medical complications from re-biopsy or treatment delay as well as additional social and financial support, which is not always available for veterans. A recent study reported that up a one third of veterans with NSCLC containing highly actionable mutations were not prescribed targeted treatment, among which, 25% of patients do not have a documented molecular testing results. Herein, we reported a pathologist-driven protocol to enhance the implement of molecular testing on guiding NSCLC treatment in veteran population. Methods: A pathologist-driven molecular testing protocol is applied West Los Angeles VA hospital since 2018. First, in preparation for diagnosis and molecular testing, tissue block will be cut in serial sections in the following priority: 2 slides for H&E, 4 slides for IHC, 2 slides for PD-L1 staining. An additional slide is made for quality control (QC) purpose before 10 additional slides are cut for molecular testing and 6 for FISH studies. The reminder of the tissue block will be cut in serial sections and preserved in a vial along with tissue shaved at initial block effacement. Every tissue block will be exhausted. Upon initial evaluation of H&E slides, the reviewing pathologist, independent of the treating oncologist, will order molecular testing including EGFR, ALK, ROS and BRAF by NGS if NSCLC is identified. PD-L1 IHC staining is also ordered automatically regardless of the histology. If a clinically actionable mutation is detected, a mutation notification is immediately sent via email by the molecular pathologist to alert the treating oncologist. Results: After implementing this protocol, we observed a decreased rate of QNS (~30% reduction) and subsequently the need for 2ndbiopsy dropped substantially. We also observed a faster TAT between initial cancer diagnosis (within 7 days) and the resulting of molecular testing to guide subsequent treatment. Conclusions: Refined tissue processing and pathologist driven ordering system can significantly impact initial management of patients with NSCLC as it reduces the rate of QNS and repeat biopsy/TAT. This protocol can be easily implemented in VA system or other community based healthcare system.

Treatment and survival of de novo metastatic hormone sensitive prostate cancer among African American US Veterans.

5079 Background: Combinations of androgen deprivation therapy (ADT) plus docetaxel (DOC) or androgen signaling inhibitors (ASIs: abiraterone, enzalutamide, etc.) have revolutionized treatment of metastatic hormone sensitive prostate cancer (mHSPC), particularly for high volume disease. However, little is known about the use of and outcomes of combination therapy in African Americans (AA) with de novo mHSPC, due to their lack of representation in clinical studies. This study evaluates the patient characteristics, treatment, and survival in a cohort of US veterans with mHSPC with equal access to treatment under the Veterans Affairs Health System (VA). Methods: Veterans with mHSPC were identified from 2014-2022 in the VA using the initial pathological diagnosis of prostate cancer with SEER stage ‘distant’ and first ADT initiated within 1 month prior and 3 months after diagnosis. Therapies including DOC or ASIs were collected if initiated from 1 month prior to 4 months after ADT. Additional information at the time of diagnosis was collected including Prostate Specific Antigen (PSA), race from VA enrollment, and Charlson Comorbidity Index (CCI). Median survival was obtained for each group and stratified by PSA level >100 ng/mL. Chi-square and ANOVA testing were used differences in survival (OS) were assessed by log-rank testing. Results: 4,248 veterans with de novo mHSPC were identified, 1138 (26.8%) were AA and 3110 (73.2%) white. Black veterans were younger (70.8 vs. 74.8, p<0.001) and had higher median PSA (183 vs. 86.3, p<0.001) with similar mean CCI (4.4 vs. 4.4, p=0.78). AA veterans were likely to have a PSA >100 ng/mL at diagnosis (61.6% vs. 46.1%, p<0.001) and to receive combination therapy than white veterans (36.8% vs. 32.7%, p=0.01). The median OS among AA and white veterans was similar (32.5 months vs. 32.1, p=0.75). In 2,120 veterans with PSA>100 ng/mL (a surrogate for higher volume disease), AA veterans were more likely to receive combination therapy (39.5% vs. 32.9%, p=0.003) without differences in survival in AA veterans compared to white (31.0 vs. 26.9 months, p=0.18). Conclusions: In an equal access health care system, AA veterans had similar survival to white veterans despite having double the PSA levels, reflecting higher risk disease. AA presented 4 years younger and are likely treated with doublet therapy. The differences in the age of onset and burden of disease highlight persistent differences in populations with mHSPC. Further investigations to understand environmental, social, and tumor factors are warranted to explain these disparities. [Table: see text]

Breast Self-Examination: An Early Familiar Diagnostic Test of Breast Cancer

Background: Among female patients’ breast cancer are a growing threat for over a century. In women, breast cancer is the most common malignancy universally such as 154 of 185 nations. Breast self-examination (BSE) is a simple, very low-cost, non-invasive early detection method used to detect early breast cancer, which involves the woman herself looking at and feeling for any change in their breast as early as possible, which yields a better survival rate. BSE should be done for all women older than 20 years. This study intended to determine knowledge, attitude, and practice (KAP) of breast cancer among medical and non-medical undergraduate students. Material & Methods: A descriptive cross‑sectional study was conducted from October to November 2019 to assess the knowledge, attitude, and practice of BSE. The target population consisted of undergraduate female medical and non‑medical students. A total of 154 (N=154) undergraduate female students participated in this study. Verbal consent was taken before recruiting the study population. Completed data forms were reviewed, edited, and processed for computer data entry. The data analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 25.0. Results: Among the study population (N=154) with an early familiar diagnosis of breast cancer ”breast self-examination, the mean age of them was 20.434±4.38. Of seventy-eight respondents (n=78), breast cancer screening test was heard by around half of the medical students (42, 53.8%) & of seventy-six non-medical respondents (n=76), around three-fifth of them (46, 60.5%) did not hear about breast cancer screening test. There was no significant relationship between them (p=0.394). Forty medical students (40, 51.3% and twenty-five non-medical students (25, 32.9%) had no idea, twenty-four medical students (24, 30.8%) & forty-three (43, 56.6%) non-medical students had monthly BSE done. Conclusion: Initial diagnosis and treatment of breast cancer have a definite survival benefit. So early detection is an issue of necessity to be uplifted. The results of the present study suggested that knowledge regarding breast cancer, its risk factors, sign symptoms, prevention measures, and performance of BSE is insufficient.

Treatment and treatment-related toxicity following subsequent breast cancer: A report from the Childhood Cancer Survivor Study (CCSS).

10051 Background: Long-term survivors of childhood cancer are at high risk for treatment-related breast cancer and have elevated mortality risk after a breast cancer diagnosis than the general population. There is no standard of care for women with treatment-related breast cancer, and treatment patterns and risk for toxicity are not known. Methods: Female survivors in CCSS diagnosed and treated for childhood cancer between 1970-1999 who developed a subsequent breast cancer (N = 344) were matched with females with sporadic breast cancer (multi-institution sampling; 1:1 matching ratio) on age at breast cancer diagnosis, breast cancer treatment decade, race/ethnicity, histology, and hormone receptor status. Conditional logistic regression evaluated univariate associations with treatments, toxicities, and synchronous breast cancer (≤12 months from diagnosis). Hazard ratios (HR) for metachronous disease risk ( > 12 months from diagnosis) were estimated using proportional hazard models with robust variance estimation. Results: Among survivors, the median time between the primary cancer and initial breast cancer diagnosis at median age 40 years (IQR 35-45) was 26 years (IQR 21-30). Two-thirds received chest radiation therapy (RT) and 44% were treated with anthracyclines for their childhood cancer. In the matched sample, breast cancer clinical features were similar between survivors vs. controls, but the odds of synchronous bilateral disease at diagnosis was 4.8-fold greater (95% CI 2.2-10.2) among survivors. Surgical interventions (99% vs. 98%, P = 0.22) and treatment with chemotherapy (46% vs. 45%, P = 0.43) were similar between groups. However, women with sporadic breast cancers were more likely to receive RT (OR 4.4, 95% CI 2.9-6.8) or anthracyclines (OR 2.4, 95% CI 1.5-3.8). Survivors were more likely to undergo mastectomy (OR 3.0, 95% CI 2.1-4.2) and experience surgical complications (OR 2.2, 95% CI 1.4-3.4), and had 1.4-fold greater odds (95% CI 1.01-1.98) of experiencing any treatment-related toxicity compared to controls. The 15-year cumulative incidence of developing a metachronous breast cancer was 20% (95% CI 13-25%) in survivors versus 9% (95% CI 5-13%) in controls (P < 0.001). Risk of metachronous disease remained higher among survivors (HR 2.4, 95% CI 1.5-4.0) after adjusting for breast cancer treatments (mastectomy, RT, and anthracyclines). Conclusions: Female survivors of childhood cancer who develop subsequent treatment-related breast cancer are more likely to develop synchronous and metachronous breast cancer compared to controls. Despite similar biologic characteristics, survivors are treated differently from females with sporadic breast cancer and are more likely to experience treatment-related toxicities. Further study of how treatment of subsequent breast cancers and corresponding toxicities impact prognosis and survival is needed.

Impact of synchronous (sync) vs metachronous (meta) metastasis at the presentation on survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor signaling inhibitors (ARSIs).

5049 Background: Pts with sync metastatic castration-sensitive prostate cancer (mCSPC) appear to have worse survival outcomes and earlier time to developing castration resistance than pts with meta mCSPC (PMID: 33914595). However, the impact of the initial timing of metastasis on survival in the mCRPC setting is less clear. Herein, our objective was to assess the correlation between the sync/meta metastatic disease presentation and survival in real-world newly diagnosed mCRPC pts. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: confirmed diagnosis of mCRPC, treatment with ARSI (abiraterone or enzalutamide) as first-line (1L) therapy for mCRPC, and no prior exposure to ARSI in the mCSPC or localized states. The disease was considered sync if distant metastasis was diagnosed within 90 days of the initial prostate cancer diagnosis. Study endpoints: progression-free survival (PFS) was defined from the start of therapy for 1L mCRPC to progression (per PCWG-2) or death from any cause. Overall survival (OS) was defined from the start of therapy for 1L mCRPC to the date of death from any cause or censored at the last follow-up. A multivariate analysis using the Cox proportional hazards model was used, adjusting for potential confounders. Results: 323 pts (144 sync and 179 meta) were eligible and included in the analysis. Sync and meta pts had respectively similar baseline characteristics: median PSA (19.6 vs 20.8 ng/ml), liver metastasis (9 vs 12.3%), median alkaline phosphatase (97 vs 95 IU/L), and ECOG performance > 1 (9 vs 3.9%). The difference in median PFS was not statistically significant (8.2 vs. 10.7 months, HR 1.13, 95% CI 0.85-1.49, p=0.4 for sync and meta, respectively). Median OS was significantly shorter in pts with sync compared to meta (26 vs. 38.7 months, HR 1.51, 95% CI 1.11-2.08, p=0.01). In the multivariate analysis, the initial timing of metastasis remained an independent prognostic factor. Conclusions: For the first time, we report the impact of the initial timing of metastasis on mCRPC prognosis in a real-world patient population with sync disease being associated with having a poor prognosis. Initial timing of metastasis may be worth accounting for in future mCRPC clinical trials to explore its prognostic value further. These hypothesis-generating data need external validation. [Table: see text]

Secondary primary malignancy risk by ER, PR, and HER-2 status in post-menopausal women with breast cancer: A population-based analysis.

1050 Background: Breast cancer is the most commonly diagnosed cancer and second leading cause of death due to cancer in women in the United States. We aimed to determine site specific incidence of SPMs in post-menopausal women with primary BC using data from the US Surveillance, Epidemiology, and End Results (SEER-17) cancer registries. Methods: We retrospectively analyzed post-menopausal women aged 45 or older with a first primary breast cancer diagnosis between 2000 and 2019, excluding those aged 45 or younger or with non-breast cancers as their first malignancy. We defined SPMs as second malignancies occurring at least 6 months after the initial breast cancer diagnosis and calculated standardized incidence ratios (SIRs) and absolute excess risk (AER) using SEER*Stat. Statistical significance was determined using p-values <0.05 and a 95% CI assuming a Poisson distribution of SPM incidence. Results: Among 774,965 post-menopausal women ≥45 years old with primary breast cancer, 10.8% developed SPMs, with significantly increased risk compared to the general population (SIR=1.14, 95% CI=1.13-1.15, p<0.05), particularly for solid tumors (SIR=1.16, 95% CI=1.15-1.16, p<0.05) and certain malignancies including salivary gland (SIR=1.77), thyroid (SIR=1.56), endocrine system (SIR=1.56), and hematological malignancies such as ALL, ANLL, and AML (SIR>1.70). Women aged 45-59 and Black women had the highest risk for all malignancies. PR receptor-positive women had higher risk for thyroid SPMs, while PR-negative women had higher risk for SPMs in female genitalia, bones and joints, and hematological malignancies. HER-positive and triple-positive (HER ER PR) women had higher risk for thyroid and hematological SPMs, while triple-negative women had higher risk for ALL, ANLL, and AML. Conclusions: This study found that 11% of post-menopausal women with primary BC develop SPMs, with thyroid cancer being the most common. Black and older women (45-59 years) had a higher risk of developing SPMs. [Table: see text]

Characterization of visits to the emergency room by patients with colorectal cancer in the year prior to their diagnosis: A retrospective study.

e15609 Background: Colorectal cancer (CRC) is one of the leading causes of cancer death globally, with more than 0.9 million deaths annually. Despite screening programs, many of the CRC patients (pts) are diagnosed at an advanced stage, resulting in an overall 5-year survival rate of only about 60%. Enhancing the detection of CRC in pts referred to the Emergency Room (ER) could potentially improve early detection and survival outcomes. While the prevalence of initial cancer diagnoses obtained through ER admission is documented, the proportion of individuals diagnosed with CRC who visited the ER during the year proceeding their diagnosis remains unknown. This study aimed to examine the percentage of CRC pts treated at Rabin Medical Center (RMC) who visited the ER in the year prior to diagnosis and to characterize these visits. Methods: A retrospective cohort study was conducted to identify pts diagnosed and treated at RMC for histologically confirmed CRC between 2012-2022 and to characterize their ER visits in the year prior to diagnosis. Each visit was recorded by date and the number of months before diagnosis. ER visits initiated for a recent diagnosis of CRC, i.e., occurring one month before diagnosis, were excluded. Demographic and clinical information (age at ER visit, gender, stage at diagnosis, number of visits, and interval between the first visit and diagnosis) was collected and analyzed. Results: Of the 2,240 pts treated for CRC at RMC between 2012-2022, 476 (21.2%) visited an ER, at RMC (13.3%) or elsewhere (7.9%), in the year prior to diagnosis. The median age at the first visit was 72 years (range: 25-96) and 55.7% were males. Pts were diagnosed with localized, locally advanced, and metastatic disease in 134 (45.0%), 70 (23.5%), and 63 (21.1%) cases, respectively, while stage was not yet established in 31 (10.4%). Quantitative and temporal characteristics of the ER visits are presented (Table 1). Pts had on average 1.6 visits (range: 1-11) in the year prior to diagnosis; 113 (37.9%) had 2 or more visits during that year. The median interval between the first ER visit and the CRC diagnosis was 4 months (range: 2-12); an interval of 5 months or longer was observed in 127 (42.6%) pts. Conclusions: To our knowledge, this is the first report on ER visits of CRC pts in the year prior to their diagnosis. The high percentage of pts visiting the ER highlights the importance of developing screening tools at the ER level to improve early detection and survival outcomes. This is further emphasized by prevalence of repeat ER visits and long interval between the first ER visit and the CRC diagnosis in many cases. [Table: see text]

Influence of the COVID-19 pandemic on the timing of surgical triage, tumor stage, and therapy of patients with colon carcinoma

PurposeWith the onset of the COVID pandemic in Germany in March 2020, far-reaching restrictions were imposed that limited medical access for patients. Screening examinations such as colonoscopies were greatly reduced in number. As rapid surgical triage after diagnosis is prognostic, our hypothesis was that pandemic-related delays would increase the proportion of advanced colon cancers with an overall sicker patient population.MethodsA total of 204 patients with initial diagnosis of colon cancer were analyzed in this retrospective single-center study between 03/01/2018 and 03/01/2022. Control group (111 patients, pre-COVID-19) and the study group (93 patients, during COVID-19) were compared in terms of tumor stages, surgical therapy, complications, and delays in the clinical setting. The data were presented either as absolute numbers or as median for constant data.ResultsA trend towards more advanced tumor stages (T4a p = 0.067) and a significant increase of emergency surgeries (p = 0.016) with higher rates of ileus and perforation (p = 0.004) as well as discontinuity resections (p = 0.049) during the pandemic could be observed. Delays in surgical triage after endoscopic diagnosis were seen during the 2nd lockdown (02/11/20–26/12/20; p = 0.031).ConclusionIn summary, the results suggest delayed treatment during the COVID-19 pandemic, with the infection pattern of COVID appearing to have a major impact on the time between endoscopic diagnosis and surgical triage/surgery. Adequate care of colon cancer patients is possible even during a pandemic, but it is important to focus on structured screening and tight diagnosis to treatment schedules in order to prevent secondary pandemic victims.

Risk of All-Cause Dementia, Alzheimer Disease, and Vascular Dementia in Breast Cancer Survivors: A Longitudinal Register-Based Study.

Now more than two-thirds of cancer survivors are aged 65 years or older, but evidence about their long-term health is thin. Cancer and its treatments have been linked to accelerated aging, so there is a concern that aging cancer survivors have an increased risk of age-related diseases, including dementia. We examined the risk of dementia among 5-year breast cancer survivors using a matched cohort study design. We included breast cancer survivors aged 50 years and older at diagnosis (n = 26,741) and cancer-free comparison participants (n = 249,540). Women eligible for inclusion in the study were those born 1935-1975 and registered in the Swedish Total Population Register between January 1, 1991, and December 31, 2015. We defined breast cancer survivors as women with an initial breast cancer diagnosis between 1991 and 2005 who survived 5 or more years after their first diagnosis. We assessed all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD) using International Classification of Diseases codes. Survival analyses were conducted using age-adjusted subdistribution hazard models accounting for competing risk of death. We did not observe an association between breast cancer survivorship and risk of all-cause dementia, AD, or VaD. However, in models stratified by age at cancer diagnosis, women diagnosed with cancer after age 65 years had a higher risk of all-cause dementia (subdistribution hazard ratio [SHR] = 1.30, 95% CI 1.07-1.58), AD (SHR = 1.35, 95% CI 1.05-1.75), and VaD (SHR = 1.64, 95% CI 1.11-2.43) in models adjusted for age, education, and country of origin. Older breast cancer survivors who survive cancer have a higher risk for dementia than their peers without a cancer diagnosis, in contrast to earlier studies showing that prevalent or incident cancer is associated with a lower risk of dementia. With the older adult population growing rapidly and because cancer and dementia are 2 of the most common and debilitating diseases among older adults, it is critical that we understand the link between the 2.

Abstract A50: Distinguishing Mosaic Li Fraumeni Syndrome, Clonal Hematopoiesis and Incidental Myeloid Neoplasms in Patients with Solid Tumors with Pathogenic TP53 Mutations Identified by Germline Testing or Cell-Free Circulating DNA Sequencing

Abstract The incorporation of panel-based germline genetic testing for assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, prostatic and pancreatic cancer in NCCN guidelines and wide adoption of cell-free circulating DNA sequencing (liquid biopsy) for patients with advanced solid tumors has increased the identification of pathogenic TP53 variants in blood of patients with solid tumors. The variant allelic frequency (VAF) of the pathogenic variant is often used to help infer the compartment of origin (germline vs somatic) with near heterozygous (~50%) VAF favoring germline; however, when VAF is low (sub heterozygous) potential considerations include mosaic Li Fraumeni syndrome, clonal hematopoiesis, or incidental myeloid neoplasms, and determining the origin of the TP53 mutation can be a challenge with important surveillance and treatment implications. We describe a cohort of patients with solid tumors or hematologic malignancies in whom pathogenic or likely pathogenic TP53 variants of uncertain origin were identified by clinical genetic testing of peripheral blood, next generation sequencing (NGS) using an 81 gene hematologic malignancy-based panel, or cell-free DNA sequencing/liquid biopsy. In a subset of patients for whom solid tumor, adjacent normal tissue and/or bone marrow (BM) was available, immunohistochemistry for p53 protein was performed. Patients (n= 17) included 11 (61%) women and 7 (39%) men with a median age of 54 years (range 8-7) at initial cancer diagnosis, with 17 unique TP53 variants with a median VAF of 16% (range, 2-50%). The most common indication for referral for additional investigation of the TP53 origin was sub-heterozygous VAF on germline testing of blood (8/47%) or saliva (1/6%); TP53 variant identified in plasma when the concurrent solid tumor was TP53 wild-type (3/18%) followed by presence of a pathogenic TP53 variant in remission BM of patients with history of hematologic malignancies (4/24%). Additional germline testing of skin fibroblasts and/or BM examination was performed in in 9 (53%) and 8 (47%) patients, respectively. p53 IHC was performed on 3 BM biopsies and 2 solid tumor tissues. A multimodality/multidisciplinary interpretation of these results allowed appropriate classification of the TP53 variants in 12/18 patients (67%). These included Li Fraumeni syndrome (5/12; 42%); clonal hematopoiesis (5/12; 42%); donor-derived clonal hematopoiesis (1/12;8%) and therapy-related myelodysplastic syndrome (1/12; 8%) patients. Appropriate awareness and distinction of clonal hematopoiesis and potential myeloid neoplasms from mosaic germline TP53 in the setting of subheterozygous VAF identified on peripheral blood or bone marrow analyses can be challenging. Multimodality testing and a multidisciplinary approach for accurate interpretation is required. Immunohistochemical staining for p53 can be useful in making this distinction in a subset of patients. Citation Format: Sanam Loghavi, Yoheved Gerstein, Mark J Routbort, Keyur P Patel, Koichi Takahashi, Molly Daniels, Julie Moskowitz, Danielle E Hammond, Kelly Chien, L. Jeffrey Medeiros, Farhad Ravandi, Hagop M Kantarjian, Guillermo Garcia-Manero, Banu Arun, Joseph D Khoury, Courtney D DiNardo. Distinguishing Mosaic Li Fraumeni Syndrome, Clonal Hematopoiesis and Incidental Myeloid Neoplasms in Patients with Solid Tumors with Pathogenic TP53 Mutations Identified by Germline Testing or Cell-Free Circulating DNA Sequencing [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A50.

Learning from long-term adolescent and young adult (AYA) cancer survivors regarding their age-specific care needs to improve current AYA care programs.

Despite growing (inter)national awareness and appreciation, age-specific care is still not always self-evident and accepted as standard of care for adolescent and young adult (AYA) cancer patients. It is unknown whether long-term AYA cancer survivors have missed age-specific care, and if so, which survivors missed it and regarding which topics. The Netherlands Cancer Registry (NCR) identified all long-term AYA cancer survivors (aged 18-39 years at initial cancer diagnosis, 5-20 years past diagnosis) in the Netherlands, who were invited to participate in a population-based, observational, cross-sectional questionnaire study (SURVAYA study), including questions on care needs. In total, 3.989 AYAs participated (35.3% response rate). One-third of them had a need for age-specific care (33.5%), 41.2% had no need and 25.3% did not know whether they had a need. Those who had a need for age-specific care were significantly more often female, higher educated, diagnosed at a younger age, and treated with chemotherapy, radiotherapy or hormone therapy. Most frequent topics were disease and treatment (29.7%), emotions (24.1%), friends (22.6%), family and children (15.6%), fertility and pregnancy (14.8%), work and reintegration (10.5%), care not tailored (13.8%), and overarching care and life (27.7%). Palliative care (0.0%), spirituality (0.2%), death (0.7%), complementary care (0.7%), and late effects (1.3%) were mentioned least. A substantial proportion of long-term AYA cancer survivors showed a need for age-specific care, varying by sociodemographic and clinical factors, on a wide variety of topics, which could be targeted to improve current AYA care services.

Efficacy of smartphone applications to help cancer patients quit smoking: Protocol of the Quit2Heal randomized controlled trial

Cigarette smoking is highly prevalent among cancer patients in the United States (US), with up to half of cancer patients smoking at the time of their initial cancer diagnosis. However, evidence-based cessation programs are rarely implemented in oncology care, and smoking is not consistently treated in cancer treatment settings. Consequently, there is an urgent need for accessible and efficacious cessation treatments that are uniquely tailored to the needs of cancer patients. Here we describe the design and implementation of a randomized controlled trial (RCT) testing the efficacy of a smartphone app (Quit2Heal) versus a US Clinical Practice Guidelines-based app (QuitGuide) for smoking cessation among a planned sample of 422 cancer patients. Quit2Heal is designed to address cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting. Quit2Heal is based on the principles of Acceptance and Commitment Therapy, a behavioral therapy that teaches skills for accepting cravings to smoke without smoking, values-driven motivation to quit, and preventing relapse. The primary aim of the RCT is to determine whether Quit2Heal has significantly higher self-reported 30-day point prevalence abstinence at 12 months relative to QuitGuide. The trial will also determine whether Quit2Heal's effect on cessation is (1) mediated by improvements in cancer-related shame, stigma, depression, anxiety, and knowledge about the consequences of smoking/quitting; and (2) moderated by baseline factors (e.g., cancer type, stage, time since diagnosis). If successful, Quit2Heal will offer a more efficacious, broadly scalable smoking cessation treatment that could be implemented alongside existing oncology care, thereby improving cancer outcomes.

Abstract 6752: Patient (pt) characteristics, diagnostic journey, and cancer enrichment among pts with nonspecific signs and/or symptoms (s/sx) in the US community oncology setting: a real-world retrospective study

Abstract Of the >1.6 million people diagnosed with cancer in the US each year, >60% are diagnosed after symptomatic presentation, including nonspecific s/sx. These nonspecific s/sx may cause pts to undergo unnecessary diagnostic evaluation while the possibility of cancer and search for its origin is explored, causing delayed treatment and poor outcomes. Additionally, pts who do not have cancer are often subjected to various undirected/misdirected procedures due to initial cancer suspicion. Our objective was to examine pt characteristics, diagnostic journey, and cancer incidence of pts with nonspecific s/sx within The US Oncology Network. This retrospective observational cohort study included pts aged ≥40 with ≥1 of the following nonspecific s/sx in their problem list at their first visit within The US Oncology Network (index date) during the identification period from 1/1/2016 to 12/31/2020: anemia, venous thromboembolism, general malaise, weight loss, nonspecific abdominal symptoms, new and unexplained breathlessness, unexplained worsening pain, and abnormal lab test results. Pts were excluded if diagnosed with any cancer (except basal cell carcinoma and squamous cell carcinoma skin cancer) within 3 years prior to or on index date. Pts were followed longitudinally with data from electronic health records for initial cancer diagnosis (dx), death, end of study observation period, or 12 months, whichever occurred first. Demographic and clinical characteristics were assessed descriptively. 103,984 pts were identified. The median age was 65.7, 64% were female, 65% were White, 41% were obese, 47% were never smokers, and 48% were from a southern practice region. 6,774/103,984 pts (7%) were diagnosed with cancer and 6,537/6,774 (97%) with 1 primary cancer: 3,825/6,537 (59%) were diagnosed with a hematologic malignancy and 2,712/6,537 (41%) with a solid tumor cancer. Among pts diagnosed with primary solid tumors, 31% had gastrointestinal, 15% genitourinary, 15% respiratory, 13% breast, and 11% gynecologic cancer. Among pts diagnosed with cancer, median time to cancer dx after being referred to secondary care within The US Oncology Network with nonspecific s/sx was >5 wks (solid: >7 wks; hematologic: >4 wks); by 17 and 34 wks, 75% and 90% of pts received a cancer dx, respectively. Within this population of pts most frequently presenting with nonspecific hematologic s/sx and subsequent cancer dx, 40% were diagnosed with solid tumor cancers within 1 year. This speaks to the unmet need for more tools such as a multi-cancer detection test that could aid in detection of multiple cancers and faster diagnostic resolution of nonspecific s/sx. Given the impact of delayed cancer dx and timely treatment on outcomes, such a test could potentially substantially improve cancer care and diagnostic evaluations. Citation Format: Christopher Benton, Ding He, Karen Todoroff, Marie V. Coignet, Ying Luan, Kathryn N. Kurtzman, Ira Zackon. Patient (pt) characteristics, diagnostic journey, and cancer enrichment among pts with nonspecific signs and/or symptoms (s/sx) in the US community oncology setting: a real-world retrospective study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6752.

181 Evaluating the Association of Age with Acuity and Severity of Illness at Initial Clinical Presentation in Patients with Leukemia and Lymphoma

OBJECTIVES/GOALS: Adolescent and young adult (AYA) patients, diagnosed with cancer between 15 and 39 years of age, often have worse outcomes compared to younger children and older adults. We will characterize age differences in acuity and severity of illness at initial presentation, as a measure for health outcomes, in patients with new diagnoses of leukemia or lymphoma. METHODS/STUDY POPULATION: We will perform a single institution-based, retrospective analysis of a cohort of pediatric oncology patients at Children’s Healthcare of Atlanta (CHOA) who were diagnosed with leukemia or lymphoma from 2010 to 2018. Data will be abstracted from the CHOA medical record and cancer registry. We will construct a severity score, with one point for 1) admission to the Intensive Care Unit (ICU), 2) ICU-level requirements at admission, 3) stage IV or metastatic disease, and 4) white blood cell count over 100,000/microliter. We will associate this score with age at presentation using logistic regression models among patients overall and stratified by disease type. All regression models will adjust for confounders (e.g., health insurance, race and ethnicity, and local-area social vulnerability level). RESULTS/ANTICIPATED RESULTS: Previous literature has shown increased cancer incidence and mortality in AYAs compared to younger children. Therefore, we hypothesize that AYA patients with a new diagnosis of leukemia or lymphoma will have a higher acuity and severity of illness at presentation than younger patients. We conducted a pilot study analyzing acuity and severity of illness by age, race, ethnicity, and insurance status. Bivariate comparisons suggested patients aged 10 and older were as likely as those younger to have a severity score of more than 0 at diagnosis (OR=0.661 , 95% CI 0.43-1.01). However, this result was collapsed across all hematologic malignancies, did not encompass the entire cohort, and did not address possible confounders; we anticipate our estimates will be different taking these factors into account. DISCUSSION/SIGNIFICANCE: Our work will be the first steps in creating a validated tool to understand disease acuity and severity. By using this tool to characterize presentation by disease type and age, we will identify unmet needs prior to an initial diagnosis of cancer. Our findings inform strategies toward narrowing age disparities in outcomes for AYA hematologic cancers.

RADIATION DIAGNOSIS OF SEROUS CARCIONEOMA OF THE OVARY OF ENORMOUS SIZE IN A PATIENT OF POSTMENOPAUSAL AGE (CLINICAL CASE)

Topicality. Among the tumors of the female genital organs, ovarian cancer is considered one of the most common. Due to the lack of a specific clinical picture at an early stage, in more than half of cases there is a delayed detection of ovarian cancer. In view of this, an urgent problem in oncogynecology remains the timely diagnosis of ovarian cancer. The purpose of the work is to demonstrate the complexity and untimely diagnosis of ovarian cancer on the example of the presented clinical case of primary radiation diagnosis of serous ovarian carcinoma of enormous size in a postmenopausal patient. Outcomes. The article reflects some experience of domestic and foreign researchers, where the reasons that explain the late diagnosis of ovarian cancer are studied. A case from clinical practice with an analysis of the development of the clinical picture of the disease, the tactics of patient management is presented. This clinical example is an example of a belated diagnosis of ovarian cancer in a postmenopausal patient. Unfortunately, in this situation, at the time of the initial diagnosis of ovarian cancer, the tumor already had a huge size, probably because of this, the clinical picture of the disease and the objective assessment of the patient's condition were regarded erroneously. Conclusion. The analysis of this clinical example convincingly indicates that only the implementation of a complete algorithm for the complex use of anamnestic, laboratory (including tumor markers), instrumental (primarily radiation diagnostic methods, such as ultrasound, computed tomography) and other diagnostic methods is the basis for the timely diagnosis of ovarian cancer.