Prior History Of Cancer Research Articles

Impact of Health Insurance and Access to Autologous Stem Cell Transplantation (ASCT) on Racial Inequity in Overall Survival (OS) Among Patients with Multiple Myeloma (MM)

Background: Survival for patients with MM has improved in the past two decades, largely attributed to the advent of novel therapies and increased use of autologous stem cell transplantation (ASCT). However, questions remain whether African Americans/Blacks (AAs) have benefitted equally from survival improvement compared to whites. Few studies have examined the simultaneous impact of health system inequities ( i.e. insurance, access to ASCT) on differential outcomes by race. We addressed these knowledge gaps using the real-world data of the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Methods: We included 5722 patients newly diagnosed with MM between January 1, 2011 and December 1, 2021. The study was limited to those with known state of residence, diagnosed in the community oncology setting, had available first-line therapy and insurance data. Longitudinal insurance data included the start and end dates of documented insurance coverage which were used to determine the insurance type at time of initial MM diagnosis. Insurance was grouped as Private, Medicare (± private or non-Medicaid government programs), any Medicaid, or Other (non-Medicaid government program ± unknown payer type). Follow-up was from diagnosis until death or last known activity in the EHR, to December 31, 2022. Patients with del(17p), t(14;16), t(4;14), or amp(1q21) were considered to have high cytogenetic risk (CR); standard risk otherwise. Dates of Medicaid expansion adoption by states were obtained from public data. Missing data on International Staging System (ISS), CR, and insurance type at diagnosis (missingness: 40%, 59%, 19%, respectively) were multiply imputed 10 times. Multivariable step-wise Cox regression was used to examine the effects of race, ASCT, and insurance on OS, treating ASCT as time-varying covariate. For access to ASCT as outcome, we used Fine-Gray subdistribution hazard regression taking death as competing risk. Covariates considered in the multivariable model included: ISS, CR, age at diagnosis, sex, and prior history of cancer. Results: Median age (range) at diagnosis was 70.5y (24 - 85); 32% were <65y at diagnosis; 54% were male; 24% were AA. Median follow-up was 2.9y (0.01 - 12). Compared to whites, AAs were more likely to be diagnosed at a younger age (median, 67y vs 71y), have less aggressive disease (ISS Stage I: 41% vs 31%) and standard CR (41% vs 36%), and more likely to reside in states without Medicaid expansion at time of MM diagnosis (74% vs 58%). Medicare was more common in whites (65.4% vs 50.5%) while Medicaid was more common in AAs (15.3% vs 4.4%). Impact of Insurance: Adjusted analyses showed a higher overall mortality risk in AAs compared to whites (adjusted Hazard Ratio [aHR]=1.10, p=0.042). Racial difference was abrogated (aHR=1.06, p=0.28) when the model was adjusted for insurance type. Compared to patients with Private insurance, patients with Medicare had lower mortality risk (aHR=0.78, p<0.0001) while the risk was higher (aHR=1.29, p=0.004) in patients with Medicaid or Other insurance (Medicaid/Other ). Impact of ASCT: Adjusted for disease, demographics, and insurance, mortality risk was higher without receipt of ASCT (aHR=1.73, p<0.0001). Of note, while ASCT utilization was lower in AAs compared to whites (aHR=0.70, p<0.0001, adjusted for insurance), this difference did not manifest as racial difference in OS within each insurance type (p>0.5). Impact of Insurance + ASCT: Considering the joint effects of ASCT and insurance type, mortality risk was highest for Medicaid/Other insurance without receipt of ASCT (aHR=3.05, 95% CI: 1.94 - 4.80); reference Private/Medicare with receipt of ASCT ( Figure). With the receipt of ASCT, mortality risks were not different between Private/Medicare and Medicaid/Other insurance (p=0.46). Similar trends were observed for AAs and whites. Conclusions: Adjusted for relevant risk factors, survival was worse in AAs with MM compared to whites. However, racial differences were abrogated after adjusting for insurance type. Overall, OS was worse in patients with Medicaid compared to those who had private insurance or Medicare. OS was also worse without receipt of ASCT, independent of insurance type. The highest mortality risk was seen in patients with Medicaid without receipt of ASCT. These findings provide real-world evidence of how inequity in health insurance and access to ASCT can impact MM survival.

Patterns of Care Among Adolescents and Young Adults Treated for Acute Lymphoblastic Leukemia: A Retrospective Study across Diverse US Practices

Background. Studies have demonstrated superior outcomes in adolescents and young adults (AYAs, age 15-39 years) with T-cell and B-cell/Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) who are treated using pediatric-inspired regimens (PIRs). However, some AYAs continue to be treated with non-PIR or adult regimens (ARs) that are associated with less favorable outcomes. The extent to which hospitals and physicians in the United States (US) have adopted PIRs to treat ALL in AYA patients is not known. Additionally, limited knowledge exists about factors associated with use of AR. The objective of this study was to describe patterns of care in AYAs with newly diagnosed ALL, and identify patient, physician and hospital-level characteristics associated with use of PIRs vs. ARs in these patients. Methods. This retrospective study analyzed data collected from medical charts of AYAs with ALL across varied cancer care settings in the US. Patients were identified by treating oncologists, who were board certified in the relevant specialty and had 3-40 years of post-residency practice experience. Physicians were not eligible to participate if they were associated with a pharmaceutical company or a healthcare/government agency in paid capacity. Patients were included based on the following criteria: newly diagnosed with ALL, 15-39 years at diagnosis, and treated with frontline PIR or AR between January 2016 and April 2022. Patients with a prior history of cancer were excluded. Standardized data collection forms were used by participating physicians to collect patient and clinical characteristics, treatment patterns, and site characteristics. Physicians were compensated for participation for each completed chart. Descriptive statistics (mean, standard deviation [SD], frequency, percentages) were used to describe these characteristics. Chi-square and multivariate logistic regression analyses were conducted to evaluate potential associations of these variables with AR use. The study received IRB (Advarra, Inc.; IRB#: 00000971) exempt status. Results. The analytic sample consisted of 378 eligible patients. Patients were treated by 178 physicians, of which 16.8% were pediatric oncologists, 59.3% were adult oncologists, and 23.9% treated patients of all ages. The majority of patients were treated at adult centers (82 [21.1%]) or centers that treat patients of all age groups (279 [71.7%]); 24 patients (6.2%) were treated at pediatric centers. Approximately three-quarters (73.8%) were treated at academic centers and one quarter (26.2%) at community centers. Of the 378 patients, 230 (61%) patients were treated with a PIR and 148 (39%) with an AR. The proportions were similar for both B-cell/Ph- patients (71.3% and 28.3%, respectively) and T-cell phenotypes (46.5% and 53.4%, respectively). Children's Oncology Group (COG)-based protocols were the most common PIR used (60.4%) followed by CALGB 10403 (23%). Among those receiving ARs, HyperCVAD-based regimens was most commonly used (n=125 [84.7%]). Of patients receiving HyperCVAD, 85.6% did not receive any immunotherapy. In univariate analyses, the use of an AR was significantly higher in subgroups of older AYAs (20-39y), males, and patients with public insurance. AYAs who were obese, had CNS involvement at diagnosis, T-cell immunophenotype, Ph+, Ph-like, or early T-cell precursor (ETP) were associated with AR use. Patients treated at non-pediatric centers, small-medium size hospitals (<500 beds), or those treated by non-pediatric oncologists (those who treat adult only or both adult and pediatric patients) were more likely to receive AR (Table 1). In multivariate analysis, patient factors independently associated with use of an AR included older age, obesity, Ph+, and Ph-like. Patients treated at small/medium size hospitals or non-pediatric centers were also significantly more likely to receive an AR vs. PIR (Table 2). Conclusions. The study provides “real-world” insights into treatment approaches used for AYAs with ALL across diverse cancer care settings. Nearly one-half of AYAs with T-cell ALL and one-third of AYAs with B-cell/Ph- ALL received AR. Additional studies are needed to understand the reasons behind the limited uptake of PIR, especially among older AYAs and in smaller and adult treatment settings.

Assessing the Impact of Marginalization on Survival for Patients Undergoing Autologous Stem Cell Transplant in Ontario, Canada

Background Autologous hematopoietic stem cell transplants (ASCT) are potentially life-saving interventions used to treat hematologic disorders. However, it is unclear if socioeconomic disparities impact the patient benefit from ASCT. Recent evidence suggests lower rates of ASCT for patients living in rural settings and for ethnic minority groups. Few population-based studies have assessed comprehensive indices of marginalization as predictors of outcomes after ASCT. In a publicly funded healthcare setting, it is crucial to understand if various aspects of marginalization interact to ultimately impact survival for patients undergoing ASCT. Methods We performed a retrospective population-based study using administrative healthcare databases from Ontario, Canada. Patients were included if they had undergone auto-SCT for lymphoma or myeloma between 2010 and 2022. The Ontario Marginalization Index (ON-Marg), created using Canadian census data, explores four key aspects of marginalization: residential instability (referring to housing instability), material deprivation (referring to individual and community abilities to access basic material needs), dependency (referring to lack of income from employment), and ethnic concentration (referring to individuals who are recent immigrants or belonging to a visible minority group). The primary outcome was 2-year overall survival (OS) from time of transplant to death or end of the study period stratified by ON-Marg quintiles. Multivariable Cox regression analyses were used to identify baseline characteristics associated with OS. Results A total of 1886 patients underwent ASCT for lymphoma and 2842 patients underwent ASCT for myeloma. The median age of patients undergoing ASCT for lymphoma was 56 years (IQR 44-63) and 64% of patients were male. 22% of patients had high aggregated diagnosis group (ADG) comorbidity scores and 15% had a prior history of cancer. 2-year OS for patients in the fifth quintile of marginalization of the ethnic concentration index was 80.4% (95% CI 75.9-84.1%), compared to 72.3% (95% CI 67.5-76.5%) in the first quintile ( Figure 1A). This survival advantage (HR 0.71, 95% CI 0.52-0.99) persisted after adjusting for age, comorbidity burden, and distance to hospital ( Table 1). Patients who lived 150-200 km from the transplant center had a lower risk of death compared to patients who lived within 50km of the hospital (HR 0.53, 95% CI 0.30-0.94). 2-year OS was not significantly different for patients in quintile 5 of marginalization of the dependency index compared to quintile 1 (HR 1.25, 95% CI 0.93-1.67), with similarly no significant difference across residential instability or material deprivation. The median age of patients undergoing ASCT for myeloma was 61 years (IQ 55-66), and 25% of patients had high ADG comorbidity scores. OS was not significantly different across all domains of marginalization, with a 2-year OS of 88.8% (95% CI 85.8-91.2%) in quintile 1 of ethnic deprivation and 87.5% (95% CI 84.7-89.8%) in quintile 5 ( Figure 1B). Higher comorbidity scores were associated with an increased risk of death compared to lower comorbidity scores (HR 2.17, 95% CI 1.58-2.98), as shown in Table 1. Living 150-200 km from the transplant center was associated with worse OS (HR 1.74, 95% CI 1.24-2.45). Conclusion This is one of the first studies to examine the effect of marginalization on outcomes after ASCT in a publicly-funded healthcare system. For patients undergoing ASCT for lymphoma, patients in quintile 5 of ethnic concentration had improved 2-year OS compared to patients in quintile 1. One possible explanation is the healthy immigrant effect, whereby immigrant patients are healthier than their Canadian-born counterparts. Cultural factors may also have a protective role. Patients undergoing ASCT for lymphoma who lived farther from the transplant center had a lower risk of death; these patients may be more highly selected based on fitness and disease biology to be referred for transplant compared to patients who live within close proximity. For patients undergoing ASCT for myeloma, 2-year OS was not affected by ethnic concentration quintile. The decision for referral for ASCT for myeloma is not as subjective, with ASCT commonly used in the first-line setting for eligible patients regardless of distance, which likely accounts for this difference. Further work is needed to ensure that all eligible patients receive ASCT.

Somatic Mutation Screening in Adult Patients with Myeloid Malignancies Provides Insights into Likely Germline Variants

Introduction Emerging evidence has shed light on the prevalence of germline variants (GV) that increase the risk of myeloid neoplasms in adults. Despite the use of next-generation sequencing (NGS) in the diagnostic workup of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), establishing a standard-of-care approach to screening patients for GV has been difficult due to a rapidly evolving list of candidate variants and inconsistent referral patterns for confirmatory testing. Here we describe our efforts to characterize molecular features at diagnosis and in remission based on tumor-only sequencing for patients with possible germline predisposition syndromes to myeloid neoplasms. Methods We retrospectively analyzed molecular pathology records of adult patients treated at the University of Pennsylvania who were diagnosed with AML and/or MDS between 2013 to 2022, had somatic NGS performed with diagnostic bone marrow biopsy, and had identified variants in genes affiliated with known or emerging MDS/AML germline predisposition syndromes. These variants (Fig. 1A) were based on those defined in ELN 2022 as well curated from the hereditary hematologic malignancy panel at the Children's Hospital of Philadelphia . Analysis focused on pathogenic and likely pathogenic variants. Results We reviewed records from 364 patients with a diagnosis of AML (n=311), MDS or MDS/MPN overlap (n=48), or other myeloid neoplasm (n=5). Median age of diagnosis was 66 years (range 21-92 years) with 11% <40 years and 15% <50 years; 56% were male, and 44% were female. Data on race and ethnicity were collected for 331 patients, which reflected demographics typically seen at our center: 86% White, 13% Black, 1% Asian/Pacific Islander, and 4% identified as Hispanic/Latino. Family history data were collected for 316 patients: 13% with hematologic malignancy and/or unexplained cytopenias, 50% with solid tumors, and 2% with a previously known germline predisposition syndrome. 31% of patients had a prior personal history of a non-myeloid cancer. Possible germline-associated variants in our cohort were most frequently seen in TP53 (n=93), RUNX1 (n=49), KRAS (n=48), and PTPN11 (n=47). Only 5 patients had undergone confirmatory exome sequencing via fibroblast culture (2 DDX41, 1 GATA2, 1 TP53, 1 CBL), so we considered patients with a baseline variant allele frequency (VAF) of 30-60% (n=161) on diagnostic studies to have possible GV (PGV) (Fig. 1A). Of these patients, 125 received frontline treatment with intensive chemotherapy (49%), HMA/venetoclax (29%), or HMA or other low-intensity therapy (23%). NGS was performed in remission for 53 patients, of whom 22 (42%) patients had persistence of their previously identified variant, which we classified as likely GV (LGV); 20/22 patients with LGV had persistence of germline-associated VAF >40% in remission. Approximately 6% of patients were <40 years of age in the PGV and LGV groups. The most frequent LGV were DDX41 (18%), CEBPA (14%), NF1 (9%), BRCA1 (9%), and RUNX1 (9%). Within the LGV cohort, 31% of patients had complex cytogenetics; 61% of patients were classified with ELN 2022 adverse risk or IPSS-R high/very high-risk disease; 64% of LGV patients had a family or personal history of cancer or unexplained cytopenias. Median OS was 18 months for both the PGV and LGV groups (Fig. 1B). When examining co-occurring somatic mutational patterns in the LGV group, we most frequently observed alterations in canonical AML/MDS-associated genes, including ASXL1, FLT3, IDH1/2, NPM1, TET2, and splicing factors. Conclusions As the acknowledgement of germline predisposition syndromes increases, it is imperative that suspected GV are recognized by laboratories and clinicians so patients can appropriately be referred for genetic counselling and confirmatory testing. Although confirmatory sequencing in unaffected tissue is considered the gold-standard approach for diagnosis, use of other factors like VAF and persistence of mutational burden in remission can help identify patients with LGV. Indeed, in our cohort, 6% of patients were considered to have LGV, of which 64% had a family or personal history of cancer or unexplained cytopenias. Limitations include the evolution of our somatic sequencing panel throughout the time course evaluated, inability to exclude somatic reversion due to somatic mutational screening only, and exclusion of variants of uncertain significance.

Confirmed Pathogenic Germline Variants in Cancer Predisposition Genes Incidentally Detected in Somatic Genomic Profiling of Multiple Myeloma Patients

Introduction: We previously showed that ~10% of patients with multiple myeloma (MM) carry pathogenic or likely-pathogenic (P/LP) germline variants (PGVs) in known cancer predisposition genes, and that moderate/high-penetrance PGVs in DNA repair genes may be associated with MM risk and favorable response to alkylating chemotherapy. Increasingly applied in MM, genomic profiling by next-generation sequencing (NGS) can identify prognostically-relevant and therapeutically-actionable somatic mutations, but it may also incidentally unveil PGVs, which can have significant implications for patients and their families. We here test the diagnostic accuracy of a novel referral tool designed to flag likely PGVs warranting confirmatory germline testing among mutations identified in somatic NGS studies of 1161 MM patients from our institution. Methods: We retrospectively reviewed 1715 commercial NGS reports of 1161 MM patients treated at the Icahn School of Medicine at Mount Sinai (ISMMS) between 2015 & 2022 (targeted 448-gene somatic profiling panels performed by a single genomic testing company for clinical purposes on bone marrow aspirate samples). In collaboration with certified genetic counselors at our institution, we applied evidence-based criteria to develop a tool to flag P/LP variants of likely germline origin warranting a referral for confirmatory germline testing (“Likely PGVs”). The resulting referral tool flags variants detected in 35 well-established cancer predisposition genes at a variant allele frequency (VAF) of >10%, as well as 24 cancer predisposition founder variants at any VAF. Next, we tested the positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity of our approach for the detection of true PGVs by analyzing paired germline whole-exome sequencing (WES) in 382/1161 (33%) MM patients in the study cohort. Germline WES data were generated for research purposes using a clinically-validated pipeline for PGV detection and annotation. Results: 385 P/LP variants were reported in somatic NGS studies of 382 MM patients who had paired somatic/germline sequencing data. Of these, 38/385 (9.9%) were found to be true PGVs in confirmatory germline testing. True PGVs detected in more than one gene included nine APC, seven CHEK2, five BRCA1, three BRCA2, three ATM and three MUTYH variants. The referral tool flagged 41/385 (10.6%) of the cohort's somatic variants as likely PGVs, identifying 32/38 (84.2%) true PGVs. The six PGVs missed by the referral tool were detected in the following genes: one APC, one CHEK2, one MITF, one MUTYH, one NF1 and one SHDA variant. In contrast, the nine variants that were mislabeled as likely PGVs but were in fact somatic were: two ATM, two BRCA2, two TSC1, one CHEK2, one BRIP1, and one RET. With a variant allele threshold of >10%, the tool had a PPV of 78.0% and a NPV of 98.3% for the detection of true PGVs. The sensitivity and specificity were 84.2% and 97.5%, respectively. Among the 692/1161 MM patients who did not have confirmatory germline testing (67%), the proportion of variants flagged as likely PGVs was very similar to that of the paired somatic/germline group (77/696, 11.1%), and variants were detected in similar genes. Assuming a PPV of 78%, 60 of these variants could represent true PGVs. Conclusion: A novel tool designed to flag likely PGVs among mutations identified in somatic genomic profiling of MM patients had high sensitivity and specificity for the detection of true PGVs. 9.9% of all MM patients with paired somatic/germline testing were found to have a true PGV, validating the results of our prior study and once again highlighting the need to implement screening strategies in high-risk subgroups of MM patients, such as those with strong family history of cancer or prior personal history of cancer.

A Nasal Swab Classifier to Evaluate the Probability of Lung Cancer in Patients With Pulmonary Nodules

Accurate assessment of the probability of lung cancer (pCA) is critical in patients with pulmonary nodules (PNs) to help guide decision-making. We sought to validate a clinical-genomic classifier developed using whole-transcriptome sequencing of nasal epithelial cells from patients with a PN≤ 30mm who smoke or have previously smoked. Can the pCA in individuals with a PN and a history of smoking be predicted by a classifier that uses clinical factors and genomic data from nasal epithelial cells obtained by cytologic brushing? Machine learning was used to train a classifier using genomic and clinical features on 1,120 patients with PNs labeled as benign or malignant established by a final diagnosis or a minimum of 12months of radiographic surveillance. The classifier was designed to yield low-, intermediate-, and high-risk categories. The classifier was validated in an independent set of 312 patients, including 63 patients with a prior history of cancer (other than lung cancer), comparing the classifier prediction with the known clinical outcome. In the primary validation set, sensitivity and specificity for low-risk classification were 96%and 42%, whereas sensitivity and specificity for high-risk classification was 58%and 90%, respectively. Sensitivity was similar across stages of non-small cell lung cancer, independent of subtype. Performance compared favorably with clinical-only risk models. Analysis of 63 patients with prior cancer showed similar performance as did subanalyses of patients with light vsheavy smoking burden and those eligible for lung cancer screening vsthose who were not. The nasal classifier provides an accurate assessment of pCA in individuals with a PN≤ 30mm who smoke or have previously smoked. Classifier-guided decision-making could lead to fewer diagnostic procedures in patients without cancer and more timely treatment in patients with lung cancer.

Prostate Specific Antigen Screening on a Nationwide Level: Featuring the Contribution of Race and Life Expectancy in Decision Making

BackgroundEstimation of life expectancy (LE) is important for the relative benefit of prostate specific antigen (PSA) screening. Limited data exists regarding screening for Black men with extended LE. The aim of the current study was to assess temporal trends in screening in United States (US) Black men with limited vs. extended LE, using a nationally representative dataset. Materials and MethodsUsing the National Health Institution Survey (NHIS) 2000 to 2018, men aged ≥40 without prior history of prostate cancer (PCa) who underwent PSA screening in the last 12 months were stratified into limited LE (ie, LE <15 years) and extended LE (ie, LE≥15 years) using the validated Schonberg index. LE-stratified temporal trends in PSA screening were analyzed for all men, and then in Black men. Weighted multivariable analyses and dominance analyses identified the predictors of PSA screening. ResultsPSA screening declined over the study period both for all eligible men with limited and extended LE, particularly between NHIS 2008 and 2013 (27.9%-20.7% in the extended). Screening increased significantly in Black men with extended LE (17.6% in 2010-25.7% in 2018). However, LE was not an independent predictor of screening in the Black cohort. Prior recipient of colonoscopy (55%-57%) and visit to health care provider (24%-32%) were the most important determinants for screening. ConclusionFor US men with extended LE, only 1 in 4 receive PSA screening, with a decline over the study-period. Screening rates increased for Black men. However, these changes were not driven by LE consideration itself, but participation in other screenings and access to a provider.

Abstract 17945: Characterization and Treatment of Primary Cardiac Rhabdomyosarcoma in the Last Three Decades

Introduction: Cardiac rhabdomyosarcomas are rare, aggressive neoplasms comprising 5% of cardiac sarcomas overall. Due to the low prevalence, there is little consensus on the appropriate identification and treatment of this condition. This research aims to characterize trends in the clinical presentation of the disease and identify improvements for therapeutic management. Methods: A literature review was conducted by identifying cases of primary cardiac rhabdomyosarcoma published in English to PubMed between 1993 and 2023 and available via the SUNY Downstate Library. Studies were analyzed for patient demographics, clinical course, treatment, and recovery. Results: The analysis included 31 identified cases. Most cases were reported in male (52%) adults (87%) with an average age of 44 (STD: 21). Patients frequently presented with dyspnea (59%) and cardiac issues (52%), including chest pain (19%) and conduction disorders (19%). Tumors were detected via echocardiogram (79%) and CT (18%) and frequently left-sided (60%), with the most cases arising in the left atrium (47%). There was valvular involvement in 43% of cases. Surgery was performed in 86% of patients, of which 33% were fully resected via sternotomy and 13% were cardiac transplants for unresectable tumors. 56% of patients survived at 12 months follow-up. Surgical management was combined with chemotherapy (46%), such as the VAC regimen (40%), and radiation (14%), which improved patient 1-year mortality by 26%. 26% of patients developed recurrence of the primary tumor and 42% of patients developed metastatic disease; osseous metastases (38%) were the most common. 13% of patients had a prior history of cancer. Conclusions: The rare rhabdomyosarcoma may present as a middle-aged patient with dyspnea and cardiac concerns refractive to standard management. A left atrial mass mimicking a benign lesion such as a myxoma may be seen on echocardiogram, and suspicious lesions should undergo surgical resection to relieve symptoms and confirm the diagnosis. Supplementation of surgical management using chemotherapy and radiation may improve outcomes in patients. Clinicians should closely monitor the patient for osseous and lung metastases. A prior history of cancer may be a risk factor for the disease.

Early detection of lung cancer through programmatic management of pulmonary nodules in the Mississippi Delta.

126 Background: Lung cancer (LC) causes the most cancer deaths in the US, but early detection improves outcomes. Uptake of Low-Dose CT screening (LDCT) has been low, contributing to race-based disparities. Programmatic management of incidentally detected pulmonary nodules (PN) provides a complementary avenue for early detection which could address disparities. In our PN cohort, Detecting Early LC in the Mississippi Delta (DELUGE), we provide broad access to early detection across a region fraught with geographic, socioeconomic, and race-based disparities. However, many detected PN will not result in LC. After successful implementation at the program level, we seek to evaluate individual-level factors important for early-detection. We evaluated how individuals with small PN identified in DELUGE differ between those who were and were not diagnosed with LC. Methods: DELUGE is a prospective cohort study where we systematically manage incidentally detected PN with trained navigators and evidence-based risk stratification. We constructed DELUGE in a community-based healthcare system across the mid-south with some of the highest per-capita LC incidence and mortality rates in the US. We evaluated all PN ≤30mm in DELUGE from 2015-2022. We compared clinical and demographic characteristics between individuals who were or were not diagnosed with LC within 24 months. Primary analysis used logistic regression, reporting odds ratios (OR) with 95% confidence intervals. Results: From 2015-2022, 17,945 individuals with PN ≤30 mm (71% of the total cohort of 25,339) were identified and enrolled in DELUGE. They had median age of 65 years, were 56% female, and 27% Black / 69% White. 853 (4.8%) patients were diagnosed with LC within two years. PN size significantly predicted LC diagnosis. For every 1 mm increase in nodule size the odds of LC increased by 15% (OR: 1.15 [1.14-1.16]); PN in an upper lobe (OR: 2.0 [1.7-2.2]) and those with cavitation also increased the odds of LC (OR: 2.9[1.9-4.2]). Sex, rural/urban residence, and number of PN were not associated with LC. The most predictive individual level characteristics were age, prior cancer history (OR: 1.3 [1.1-1.5], family cancer history (OR: 1.7 [1.5-2.0], COPD (OR: 3.3 [2.9-3.8]), and smoking history (OR: 6.6 [5.3-8.4]). In the multiple variable model, the most significant associations with LC diagnosis included PN size, age, insurance, family cancer history, COPD, and smoking history (all p&lt;0.0001). This model could provide estimated sensitivity 0.81 and specificity 0.81 for predicting LC (AUC= 0.88). Conclusions: Factors measurable at baseline have predictive ability, and predictive modeling may be useful in management of small PN. More focused follow-up could improve programmatic efficiency, targeting the alleviation of geographic, socioeconomic, and race-based health disparities in this high poverty region of the US.

Empowering women’s health: Opportunity to bridge breast cancer screening to lung cancer screening.

121 Background: Lung cancer (LC) is the leading cause of cancer-related death for women in the United States (US). It surpasses the combined mortality rate of breast, cervical and ovarian cancers. Early detection of LC at stage I increases the 5-year survival rate to 80%. Lung Cancer Screening (LCS) is an effective tool for early detection. However, while 78% of women over 50 in the US undergo Breast Cancer Screening (BCS), only 6% of eligible women receive LCS. Methods: This is a retrospective study of all women diagnosed with primary LC presenting to Indiana University Simon Comprehensive Cancer Center from January 2019 to December 2020. We collected sociodemographic characteristics and information related to smoking history, LCS and BCS. We excluded patients with a prior history of lung or breast cancer who were under surveillance, and those with unknown smoking history. We assessed the BCS and LCS eligibility and utilization according to the U.S. Preventive Services Task Force latest recommendations. We also determined the utilization of LCS in women who have received BCS. Results: Among the 307 women who met the eligibility criteria, 87.6% were white, 51.8% had a Medicare insurance, 41.7% were ever-smoker, and 64.5% had advanced stages of LC (Stage II-Stage IV). Approximately half of our cohort was eligible for LCS, but only 20% received LCS. On the other hand, 72% were eligible for BCS and 58% of them underwent BCS. Among women who received BCS and were eligible for LCS, only25% underwent LCS. The median time from BCS to LC diagnosis was approximately 2.2 years. Among the 178 women who received BCS within one year prior to LC diagnosis, 27% underwent LCS. Among the remaining women who did not have LCS,66.7% of women were already in a later stage (Stage II-IV) at the time of LC diagnosis. Conclusions: Our study demonstrates that majority of women, who met the eligibility criteria for BCS and LCS, received BCS but not LCS prior to their LC diagnosis. This shows that despite the potential mortality benefit, LCS is still underutilized. Receiving LCS at the time of BCS can provide a valuable opportunity to increase LCS participation among eligible women and the potential of diagnosing LC at earlier stages.

Donors With a Prior History of Cancer: Factors of Non-Utilization of Kidneys for Transplantation.

Cancer transmission from deceased donors is an exceedingly rare but potentially fatal complication in transplant recipients. We aimed to quantify the likelihood of non-utilization of kidneys for transplantation from donors with a prior cancer history. We included all intended and actual deceased donors in Australia and New Zealand between 1989 and 2017. Association between prior cancer history and non-utilization of donor kidneys was examined using adjusted logistic regression. Of 9,485 deceased donors, 345 (4%) had a prior cancer history. Of 345 donors with a prior cancer history, 197 (57%) were utilized for transplantation. Donor characteristics of age, sex and comorbidities were similar between utilized and non-utilized donors with prior cancer. The time from cancer to organ donation was similar between utilized and non-utilized donors, irrespective of cancer subtypes. Donors with a prior cancer history were less likely to be utilized [adjusted OR (95% CI) 2.29 (1.68-3.13)] than donors without prior cancer. Of all actual donors, the adjusted OR for non-utilization among those with prior cancer was 2.36 (1.58-3.53). Non-melanoma skin cancer was the most frequent prior cancer type for utilized and non-utilized potential donors. Donors with prior cancers were less likely to be utilized for transplantation, with no discernible differences in cancer characteristics between utilized and non-utilized donors.

Safety of pregnancy after breast cancer in young women with hormone receptor-positive disease: a systematic review and meta-analysis

Despite increasing evidence on the safety of pregnancy after anticancer treatments in breast cancer survivors, many physicians and patients remain concerned about a potential risk of pregnancy specifically in the case of hormone receptor-positive breast cancer. A systematic literature search of Medline, Embase and Cochrane library with no language or date restriction up to 31 March 2023 was carried out. To be included, articles had to be retrospective and prospective case-control and cohort studies as well as clinical trials comparing survival outcomes of premenopausal women with or without a pregnancy after prior diagnosis of hormone receptor-positive breast cancer. Disease-free survival (DFS) and overall survival (OS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Study protocol is registered in PROSPERO (n. CRD42023394232). Out of 7796 screened studies, 8 were eligible to be included in the final analysis. A total of 3805 patients with hormone receptor-positive invasive early breast cancer were included in these studies, of whom 1285 had a pregnancy after breast cancer diagnosis. Median follow-up time ranged from 3.8 to 15.8 years and was similar in the pregnancy and non-pregnancy cohorts. In three studies (n= 987 patients) reporting on DFS, no difference was observed between patients with and those without a subsequent pregnancy (HR 0.96, 95% CI 0.75-1.24, P= 0.781). In the six studies (n= 3504 patients) reporting on OS, patients with a pregnancy after breast cancer had a statistically significant better OS than those without a pregnancy (HR 0.46, 95% CI 0.27-0.77, P < 0.05). This systematic review and meta-analysis of retrospective cohort studies provides updated evidence that having a pregnancy in patients with prior history of hormone receptor-positive invasive early breast cancer appears safe without detrimental effect on prognosis.

A rare clinical presentation of lung cancer: two cases of solitary digital metastasis on Tc-99m MDP bone scan

BackgroundAcrometastases are accounted for a very small proportion of bone metastases. Lung cancer is the most common acrometastasis origin, and it often has a poor prognosis. The aim of the present cases is to describe the probability of an acrometastasis in the differential diagnosis of finger lesions and to emphasize the importance of taking local views of extremity of complaint for proper interpretation in such patients.Case presentationHere we reported two patients with metastases to the fingers with occult primary lung carcinoma and a history of prior lung malignancy, respectively. First case was a 58-year-old man with history of pain and swelling in the fourth finger of his left hand. He underwent an amputation from the metacarpophalangeal level and the pathological diagnosis was metastatic NSCLC. The second case was a 65-year-old ex-smoker man with a history of prior lung cancer (adenocarcinoma) suffered from a swollen, erythematous, painful tip of the right third finger. Phalangectomy was performed and the histological examination of the amputated part revealed the presence of a metastatic differentiated carcinoma of pulmonary origin.ConclusionsWhen assessing the masses located at fingers, possibility of a solitary metastatic lung lesion should be considered.

Secondary Breast Angiosarcoma After a Primary Diagnosis of Breast Cancer: A Retrospective Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.

Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment. Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival. Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period ( P =0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P <0.001) and 23% received chemotherapy (vs. 45% for PBA, P =0.11). We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma.

Muscle Reference Values From Thoracic and Abdominal CT for Sarcopenia Assessment: The Framingham Heart Study.

Loss of muscle mass is a known feature of sarcopenia and predicts poor clinical outcomes. Although muscle metrics can be derived from routine computed tomography (CT) images, sex-specific reference values at multiple vertebral levels over a wide age range are lacking. The aim of this study was to provide reference values for skeletal muscle mass and attenuation on thoracic and abdominal CT scans in the community-based Framingham Heart Study cohort to aid in the identification of sarcopenia. This secondary analysis of a prospective trial describes muscle metrics by age and sex for participants from the Framingham Heart Study without prior history of cancer who underwent at least 1 CT scan between 2002 and 2011. Using 2 previously validated machine learning algorithms followed by human quality assurance, skeletal muscle was analyzed on a single axial CT image per level at the 5th, 8th, 10th thoracic, and 3rd lumbar vertebral body (T5, T8, T10, L3). Cross-sectional muscle area (cm 2 ), mean skeletal muscle radioattenuation (SMRA, in Hounsfield units), skeletal muscle index (SMI, in cm 2 /m 2 ), and skeletal muscle gauge (SMRA·SMI) were calculated. Measurements were summarized by age group (<45, 45-54, 55-64, 65-74, ≥75 years), sex, and vertebral level. Models enabling the calculation of age-, sex-, and vertebral-level-specific reference values were created and embedded into an open access online Web application. The cohort consisted of 3804 participants (1917 [50.4%] males; mean age, 55.6 ± 11.8 years; range, 33-92 years) and 7162 CT scans. Muscle metrics qualitatively decreased with increasing age and female sex. This study established age- and sex-specific reference values for CT-based muscle metrics at thoracic and lumbar vertebral levels. These values may be used in future research investigating the role of muscle mass and attenuation in health and disease, and to identify sarcopenia.

Risk of developing glioblastoma following non-CNS primary cancer: a SEER analysis between 2000 and 2018.

Patients with a prior malignancy are at elevated risk of developing subsequent primary malignancies (SPMs). However, the risk of developing subsequent primary glioblastoma (SPGBM) in patients with a prior cancer history is poorly understood. We used the Surveillance, Epidemiology, and End Results (SEER) database and identified patients diagnosed with non-CNS malignancy between 2000 and 2018. We calculated a modified standardized incidence ratio (M-SIR), defined as the ratio of the incidence of SPGBM among patients with initial non-CNS malignancy to the incidence of GBM in the general population, stratified by sex latency, and initial tumor location. Of the 5,326,172 patients diagnosed with a primary non-CNS malignancy, 3559 patients developed SPGBM (0.07%). Among patients with SPGBM, 2312 (65.0%) were men, compared to 2,706,933 (50.8%) men in the total primary non-CNS malignancy cohort. The median age at diagnosis of SPGBM was 65years. The mean latency between a prior non-CNS malignancy and developing a SPGBM was 67.3months (interquartile range [IQR] 27-100). Overall, patients with a primary non-CNS malignancy had a significantly elevated M-SIR (1.13, 95% CI 1.09-1.16), with a 13% increased incidence of SPGBM when compared to the incidence of developing GBM in the age-matched general population. When stratified by non-CNS tumor location, patients diagnosed with primary melanoma, lymphoma, prostate, breast, renal, or endocrine malignancies had a higher M-SIR (M-SIR ranges: 1.09-2.15). Patients with lung cancers (M-SIR 0.82, 95% CI 0.68-0.99), or stomach cancers (M-SIR 0.47, 95% CI 0.24-0.82) demonstrated a lower M-SIR. Patients with a history of prior non-CNS malignancy are at an overall increased risk of developing SPGBM relative to the incidence of developing GBM in the general population. However, the incidence of SPGBM after prior non-CNS malignancy varies by primary tumor location, with some non-CNS malignancies demonstrating either increased or decreased predisposition for SPGBM depending on tumor origin. These findings merit future investigation into whether these relationships represent treatment effects or a previously unknown shared predisposition for glioblastoma and non-CNS malignancy.

43251 Duration of acceptable delay until subsequent full body skin examination, given prior history of skin cancer or lesions suspicious for skin cancer

43251 Duration of acceptable delay until subsequent full body skin examination, given prior history of skin cancer or lesions suspicious for skin cancer

Impact of Size Thresholds on the Diagnosis of Incidental Adrenal Lesions: A Systematic Review and Meta-Analysis

BackgroundPreferred size-threshold recommendations for management of incidental adrenal lesions remain controversial. PurposeThis meta-analysis aimed to compare the diagnostic accuracy of different size thresholds for detecting malignancy in patients with incidental adrenal lesions on imaging. Materials and MethodsA systematic review of MEDLINE, Embase, Scopus, the Cochrane Library, and the gray literature, covering the period from inception to September 2021, was performed. Studies with >10 patients evaluating the diagnostic accuracy of imaging size thresholds for detecting malignancy in patients with incidental adrenal lesions and no prior history of cancer were included. Study, clinical, imaging, and accuracy data for eligible studies were independently acquired by two reviewers. Primary meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. ResultsFrom 2,690 citations, 40 studies (9,794 patients with mean age ranging from 41 to 66 years) were included. Most (36 of 40) were retrospective single-center studies. CT with or without MRI served as the index test(s). Sensitivity and specificity values, respectively, by size threshold used in the included studies were as follows: 85% (95% confidence interval [CI] 74%-91%) and 39% (95% CI 23%-57%) for 3-cm thresholds; 85% (95% CI 78%-90%) and 75% (95% CI 62%-85%) for 4-cm thresholds; 70% (95% CI 56%-81%) and 74% (95% CI 59%-85%) for 5-cm thresholds; and 75% (95% CI 67%-82%) and 77% (95% CI 62%-87%) for 6-cm thresholds. No cause for variability in sensitivity or specificity was identified on subgroup analysis of the 4-cm threshold. Nearly half of the studies (19 of 40) had at least one QUADAS-2 domain with a high risk of bias. ConclusionsA 4-cm size threshold demonstrates the highest combined sensitivity and specificity, with a preserved specificity compared with higher size thresholds, but with a trend toward improved sensitivity. Future research reevaluating 4-5 cm size thresholds while excluding characteristically benign lesions by imaging may help redefine a size threshold that has improved specificity but preserved sensitivity, compared with the existing 4-cm threshold.

A Complex Case of Pulmonary Silico-Tuberculosis and Review of Literature.

Silicosis caused by the inhalation/deposition of free silica particles is characterized by pulmonary inflammation/fibrosis. Among the clinical disorders associated with silicosis, tuberculosis is by far the most prominent. A 66-year-old male non-smoker, originally from North Africa, reported a dry cough and significant weight loss. He was a foundry worker. He had a medical history of bladder carcinoma associated with schistosomiasis. Computed tomography (CT) and positron emission tomography (PET)/CT showed bilateral multiple hypermetabolic lung nodules, some with cavitation. The patient underwent surgical resection of the largest nodule, which was highly suspicious of lung metastasis. The histological examination revealed multiple nodular formations. Several lesions showed the characteristic features of silicotic nodules. There were also adjacent well-formed granulomas, some with central caseous necrosis. A real-time polymerase chain reaction, performed for the identification and quantification of the DNA of the Mycobacterium tuberculosis complex, was positive. Pulmonary silico-tuberculosis is often encountered in patients with a history of silica exposure in tuberculosis-endemic areas. This case serves as a reminder to never underestimate patient occupational exposure and geographic origin. A careful histological diagnosis and molecular investigation are mandatory when approaching difficult cases, especially patients with a prior cancer history and clinical/radiological features suggestive of tumour recurrence/metastasis.

Prediction of clinically significant prostate cancer using a novel 68Ga-PSMA PET-CT and multiparametric MRI-based model.

There are some limitations in the commonly used methods for the detection of prostate cancer. There is a lack of nomograms based on multiparametric magnetic resonance imaging (mpMRI) and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) for the prediction of prostate cancer. The study seeks to compare the performance of mpMRI and 68Ga-PSMA PET-CT, and design a novel predictive model capable of predicting clinically significant prostate cancer (csPCa) before biopsy based on a combination of 68Ga-PSMA PET-CT, mpMRI, and patient clinical parameters. From September 2020 to June 2021, we prospectively enrolled 112 consecutive patients with no prior history of prostate cancer who underwent both 68Ga-PSMA PET-CT and mpMRI prior to biopsy at our clinical center. Univariate and multivariate regression analyses were used to identify predictors of csPCa, with a predictive model and its nomogram incorporating 68Ga-PSMA PET-CT, mpMRI, and the clinical predictors then being generated. The constructed model was evaluated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis, and further validated with the internal and external cohorts. The model incorporated prostate-specific antigen density (PSAd), Prostate Imaging Reporting and Data System (PI-RADS) category, and maximum standardized uptake value (SUVmax), and it exhibited excellent predictive efficacy when applying to evaluate both training and validation cohorts [area under the curve (AUC): 0.936 and 0.940, respectively]. Compared with SUVmax alone, the model demonstrated excellent diagnostic performance with improved specificity (0.910, 95% CI: 0.824-0.963) and positive predictive values (0.811, 95% CI: 0.648-0.920). Calibration curve and decision curve analysis further confirmed that the model exhibited a high degree of clinical net benefit and low error rate. The constructed model in this study was capable of accurately predicting csPCa prior to biopsy with excellent discriminative ability. As such, this model has the potential to be an effective non-invasive approach for the diagnosis of csPCa.