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Background: Among the parameters that have a prognostic and/or predictive significance to therapeutic response, in the case of breast carcinoma, the study of tumor-infiltrating lymphocytes in breast carcinomas is emerging. The present study aimed to access the clinicopathological profiles of tumor-infiltrating lymphocytes in patients with primary breast carcinoma. Materials and Methods: Information was collected from the archive of the Department of Pathology, about invasive breast cancers diagnosed between April 2019 –March 2020. Hormone receptor status and Ki-67 index were assessed. For tumor-infiltrating lymphocytes, hematoxylin and eosin sections were evaluated following the guidelines of the “International Working Group for tumor-infiltrating lymphocytes in Breast Cancer—2014”. Results: High tumor-infiltrating lymphocytes were seen in 64.2% and 43.8% in ages < 50 and > 50 respectively. All cases of invasive lobular carcinoma had low tumor-infiltrating lymphocytes. 62.5% of T1 tumors were associated with low TILs whereas 80% of low tumor-infiltrating lymphocytes were T3. 71.4% of lymph node-positive tumors had low tumor-infiltrating lymphocytes. All breast cancers showed lymphocytic infiltrate. 40% of the tumors showed intermediate to high tumor-infiltrating lymphocytes. Lymphocyte-predominant breast cancers were 30%. Among the LPBC, 55.5% were triple-negative breast cancers, 33.3% were HR+, and 11.2% were HER2 positive. Conclusions: Low tumor-infiltrating lymphocytes presented at an advanced stage of the disease at the time of diagnosis. tumor-infiltrating lymphocytes in breasts decreased with increasing age. LPBCs were predominantly TNBCs. All breast cancers were immunogenic, stating the necessity to report tumor-infiltrating lymphocytes in all breast carcinomas.

Background: The term “financial toxicity” or “hardship” is a patient-reported outcome that results from the material costs of cancer care, the psychological impacts of these costs, and the coping strategies that patients use to deal with the strain that includes delaying or forgoing care. However, little is known about the impact of financial toxicity on cancer screening. We examined the effects of financial toxicity on the use of screening tests for prostate and colon cancer. We hypothesized that greater financial hardship would show an association with decreased prevalence of cancer screening. Methods: This cross-sectional survey–based US study included men and women aged ≥50 years from the National Health Interview Survey database from January through December 2018. A financial hardship score (FHS) between 0 and 10 was formulated by summarizing the responses from 10 financial toxicity dichotomic questions (yes or no), with a higher score associated with greater financial hardship. Primary outcomes were self-reported occurrence of prostate-specific antigen (PSA) blood testing and colonoscopy for prostate and colon cancer screening, respectively. Results: Overall, 13,439 individual responses were collected. A total of 9,277 (69.03%) people had undergone colonoscopies, and 3,455 (70.94%) men had a PSA test. White, married, working men were more likely to undergo PSA testing and colonoscopy. Individuals who had not had a PSA test or colonoscopy had higher mean FHSs than those who underwent these tests (0.70 and 0.79 vs 0.47 and 0.61, respectively; P≤.001 for both). Multivariable logistic regression models demonstrated that a higher FHS was associated with a decreased odds ratio for having a PSA test (0.916; 95% CI, 0.867–0.967; P=.002) and colonoscopy (0.969; 95% CI, 0.941–0.998; P=.039). Conclusions: Greater financial hardship is suggested to be associated with a decreased probability of having prostate and colon cancer screening. Healthcare professionals should be aware that financial toxicity can impact not only cancer treatment but also cancer screening.

This review aspires to summarize the landmark advancements in the management of the non-small cell lung cancer (NSCLC), both historically and contemporarily with special focus in older adults.The past two decades have witnessed remarkable improvements in the diagnosis and management of lung cancer. Screening recommendations now facilitate earlier diagnosis in high-risk individuals, PET/CT scans have improved radiologic accuracy in identifying sites of disease, and surgical management with minimally invasive techniques has rendered surgery safer in those with limited physiologic reserve. Radiation enhancements, especially radiosurgery, have extended the reach and safety of radiation among high-risk populations. Finally, the revolution in precision medicine with identification of numerous actionable mutations, the advent of immunotherapy, and enhanced supportive care have revolutionized the outcomes in patients with advanced lung cancer. Older adults who represent a majority of patients battling lung cancer have not benefitted to the same extent as their younger counterparts. This special population is only expected to grow in coming days. Hence, addressing major gaps in the management of older adults with NSCLC and optimizing the care are much needed.

IntroductionElectronic cigarette (e-cigarette) smoking and similar novel smoking modalities have raised questions about their impact on various cancers compared with traditional forms of tobacco smoking. Tobacco smoking has been proven to increase the risk of many cancers, including lung (LCa) and bladder (BCa) cancer. Currently, there is little data on how e-cigarette smoking impacts the incidence of these cancers. We investigated whether any disparities exist in the prevalence of LCa and BCa between various smoking histories using a US nationally representative data source.MethodsThis cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database between 2016-2018. Primary endpoint was self-reported occurrence of LCa and BCa diagnosis. Multivariable logistic regression analyses assessed possible association of various covariates with diagnosis of these cancers. ResultsPrevalence of BCa and LCa was higher in all smoking histories compared to never smokers. Patients with a history of e-cigarette smoking vs. no history of e-cigarette smoking were significantly younger at BCa diagnosis (56.87 [±9.86] vs. 65.00 [±12.60] years, p=0.001). Multivariable logistic regression models showed that a history of cigarette smoking and e-cigarette smoking individually and exclusively was associated with increased ORs of 2.476 (p=ConclusionsCompared to never smokers, e-cigarette smoking history was associated with increased risk of LCa and BCa development. Additional studies are needed to better define the public health effects of these novel and unregulated products.

564 Background: CDH1 mutated UBCs are characterized by plasmacytoid histology and are associated with an aggressive clinical course at the time of diagnosis. Methods: Cohort 1: 6,676 clinically advanced UBC patients (pts) underwent comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA), microsatellite instability (MSI), tumor mutational burden (TMB), and genomic loss of heterozygosity (gLOH, high ≥16%). Predominant genetic ancestry was determined using a SNP-based approach and classified as one of the 5 categories: African (AFR), European (EUR), Central and South American (AMR), South Asian (SAS), or East Asian (EAS). Cohort 2: 586 UBC pts underwent a RWCOS using the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine urothelial clinico-genomic database (FH-FMI CGDB). The de-identified data originated from approximately 280 US cancer clinics (~800 sites of care) Jan 2011-Apr 2022. Differences in real-world progression-free survival (rwPFS) and overall survival (rwOS) were evaluated by Cox proportional hazard models. Results: Cohort 1: 217 (3.3%) of UBC had a CDH1 short variant (SV) mutation with 65.2% featuring plasmacytoid histology. When compared with CDH1 wild-type (WT) UBC, the CDH1-mutated UBC had similar age, gender, and genetic ancestry. The CDH1-mutated UBC featured a higher frequency of MSI (2.7% vs 0.8%; p=.002), mean TMB (14.8 vs 9.9 mut/Mb p

PURPOSE: We investigated the association between race and FT among previous patients with cancer. Studies show that patients with cancer experience financial toxicity (FT) because of their cancer treatment. METHODS: Data on individuals with a cancer history were collected in this cross-sectional study during 2012, 2014, and 2017, from the US Health Information National Trends Survey. This survey is conducted by mail with monetary compensation as an incentive. We specifically assessed responses to two questions: Has cancer hurt you financially? Have you been denied health insurance because of cancer? Multivariable logistic regression analyses were used to assess the associations between these questions and race. RESULTS: Of 10,592 individuals participating, 1,328 men and women (12.5%) with a cancer history were assessed. Compared with Blacks, Whites were found to have a higher rate of insurance (95.4% v 90.0%), were more likely to receive cancer treatment (93.9% v 85%), and had a higher rate of surgical treatment than Blacks (77% v 60%), Hispanics (55%), and others (77%, 60%, 55%, and 74.2%, respectively, P < .001). On multivariable analysis, Blacks were more than five times as likely to be denied insurance (odds ratio, 5.003; 95% CI, 2.451 to 10.213; P < .001) and more than twice as likely to report being hurt financially because of cancer (odds ratio, 2.448; 95% CI, 1.520 to 3.941; P < .001) than Whites. Of all cancer groups analyzed (genitourinary, gynecologic, gastrointestinal, and breast), genitourinary malignancies were the only group in which the rate of reporting being hurt financially varied in a statistically significant manner (Whites 36.7%, Hispanics 62.5%, and Blacks 59.3%, P = .004). CONCLUSION: Our data suggest that race is significantly associated with FT because of cancer. Awareness of racial inequality with regards to FT should be raised among health care workers.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive malignancy with a presentation like either autoimmune diseases, drug reactions, or infections. We hereby present a unique case of AITL. A 61-year-old Caucasian male with a past medical history of chronic obstructive pulmonary disease (COPD) presented to the emergency department with a rash over his bilateral knees, shortness of breath, and productive cough of few days. He was managed for suspected COPD exacerbation associated with community-acquired pneumonia. On the day of admission patient was having an itchy maculopapular rash, ecchymosis on the left flank, and generalized lymphadenopathy. Physical exam showed generalized lymphadenopathy. Laboratory tests revealed leukocytosis, thrombocytopenia and were positive for multiple autoantibodies. Epstein-Barr virus polymerase chain reaction and hepatitis B virus core antibody were positive. Skin biopsy revealed findings suggestive of a small vessel vasculitis. Inguinal lymph node biopsy showed AITL. The patient recovered with chemotherapy. The case illustrates that clinical presentation of AITL mimics rheumatologic disorders and infections. This complexity could arise from the follicular T helper cell, which is an important checkpoint for B cell activation and differentiation. Additionally, skin involvement is one of the important findings of AITL and a variety of lesions have been reported as skin manifestations.

e17014 Background: Prostate Specific Antigen (PSA) testing can improve early prostate cancer detection. However, numerous factors can influence patients’ willingness and ability to undergo PSA testing. Methods: We performed a cross-sectional study investigating the impact of various degrees of ischemic heart disease (IHD) on PSA testing. We assessed 3,822 male respondents aged 55-75 from the 2018 year of the National Health Interview Survey (NHIS). Men were stratified according to the degree of IHD (none, history of angina pectoris (AP), history of myocardial infarction (MI), or history of neither, but with a diagnosis of IHD). Multivariable logistic regression analysis was used to assess the relationship between IHD and being tested for PSA, adjusting for known cofounders. Results: Multivariable logistic regression demonstrated that males with a history of IHD (no MI or AP) were more likely to have ever been PSA tested than males without IHD (p = 0.012, OR = 1.630, 95% CI 1.115-2.383), as seen in Table. Additionally, older age (p < 0.001), having a partner (vs. no partner p < 0.001), homosexual sexual orientation (vs. heterosexual orientation p = 0.007), and a history of cancer (vs. no history p < 0.001) all increased likelihood of being PSA tested. In contrast, Asian race (vs. White, p = 0.001), and being a current smoker (vs. no smoking history, p < 0.001) decreased the likelihood. Interestingly, males with a history of a symptomatic IHD (MI or AP) were not shown to be more likely to undergo PSA testing. Conclusions: Our results suggest that males with non-symptomatic IHD are more likely to be PSA tested. Males with symptomatic IHD do not seem to undergo more PSA screening, perhaps due to lower suggested life expectancy. Awareness of discrepancies in PSA testing in men with IHD should be raised. Table - Multivariable logistic regression analyses demonstrating relationships with likelihood of being PSA tested.[Table: see text]

e18558 Background: Research has shown that the COVID-19 pandemic has reduced access to cancer treatment and care for patients, especially for COVID-19 patients. Methods: We investigated the impact of COVID-19 testing on access to cancer care. A US based cross sectional study was conducted on 2,393 cancer patients using data from the 2020 National Health Interview Survey. Multivariable logistic regression was used to assess associations between COVID-19 testing and likelihood of receiving cancer treatment or other cancer care during the pandemic. Results: Patients who reported ever being tested for COVID were on average younger (66.9 vs 69.3, p

4568 Background: Urothelial bladder carcinomas (UBC) with genomic alterations (GA) in the Fibroblast Growth Factor Receptor ( FGFR) genes have been postulated to be less responsive to immune checkpoint inhibitors (ICI). Immune microenvironment of these tumors could be altered due to suppression of interferon signaling pathways. Here, we present comprehensive genomic profiling (CGP) of FGFR altered UBC to study the underlying immunogenomic mechanisms of response and resistance. Methods: 4,035 UBC underwent hybrid capture based CGP. Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined using 114 loci. Programmed death ligand (PD-L1) expression in tumor cells was assessed by IHC (Dako 22C3). Results: 894 (22%) of UBC featured FGFR GA ( FGFR1 3.7%; FGFR2 1.1%; FGFR3 17.4%). Gender and age distribution was similar in all groups. FGFR3 cases had lower GA/tumor and 14.7% GA were fusions. ERBB2 amplification was significantly higher in FGFR1/2 altered UBC compared with FGFR3 altered UBC. MTOR pathway GA were highest in FGFR3 altered UBC. FGFR3 altered UBC featured significantly higher frequencies of biomarkers predicting resistance to ICI including lower TMB, lower PD-L1 expression and higher frequencies of GA in MDM2. FGFR3 driven UBC also features significantly higher frequencies of CDKN2A/B loss and MTAP loss which have also recently been linked to IO drug resistance. Conclusions: UBC harboring FGFR GA have increased frequency of alterations that have been linked to ICI resistance. Further evaluation of FGFR-based biomarkers in UBC clinical trials focused on the assessment of the patient response to ICI appears warranted. [Table: see text]

21 Background: The term ‘financial toxicity’ or ‘hardship’ is used to describe the financial problems patients experience due to high out-of-pocket costs for their healthcare. Financial toxicity in the context of cancer treatment is an area of recent study due to the significant costs associated with these treatments, but little is known about the effect of financial toxicity on cancer prevention. We examined the effects of financial toxicity on the utilization of screening tests for prevalent cancers, including prostate and colon cancer, using a US nationally representative survey-based data source. We hypothesized that patients with more financial hardship would show an association with decreased prevalence of prostate and colon cancer screening. Methods: This cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database from January – December 2018. A financial hardship score between 0 and 1 was formulated by summarizing the responses from ten financial toxicity questions including if in the past 12 months one was unable to afford prescription medication or healthcare; or if one had to skip or take less medicine to save money. A higher score was associated with a worse financial hardship score. The primary outcomes of the study were self-reported occurrence of PSA blood testing for prostate cancer screening, and occurrence of colonoscopy for colon cancer screening. Results: As shown in table, a higher financial hardship score was associated with a decreased odds ratio for having a PSA test of 0.916 (95% CI 0.867-0.967, p=0.002) and colonoscopy of 0.969 (95% CI 0.941-0.998, p=0.039). Conclusions: Worse financial hardship is associated with a decreased probability of having PSA or colonoscopy screening tests. Awareness of this specific toxicity needs to be raised, examining the association of financial toxicity and screening of prostate, colon, and other additional cancers. [Table: see text]

230 Background: Prostate specific antigen (PSA) screening remains a controversial issue. However, most urological guidelines recommend PSA testing through a shared decision-making process with the patient. The rate of PSA screening in men with a history of cancer compared to men with no cancer history is not well known. We aimed to compare PSA testing in men aged 55-69 years with and without a history of cancer (excluding prostate cancer patients). Methods: Utilizing the National Health Interview Survey (NHIS) a retrospective cross-sectional study between the years 2015 and 2018 was carried out to analyze and compare PSA testing rates in men aged 55-69 years. Multivariable logistic regression model was implemented do demonstrate potential associations with PSA testing. Results: A total of 13,850 men aged 55-69 years included in the NHIS Survey were analyzed. 1519 (10.9%) men had a history of cancer (non-prostate). On multivariable analysis, men who were previously diagnosed with cancer had a higher rate of PSA testing compared to men with no history of cancer (OR: 1.88, 95% CI 1.39-2.54, p < 0.001). Other factors associated with an increased likelihood of undergoing PSA testing included: age, homosexual orientation, and married men. In contrast, current smokers, American Indians and Alaskan Natives and Asians were less likely to undergo PSA testing. Conclusions: Our data suggest that men aged 55-69 with a history of cancer are more likely to undergo PSA testing than men with no cancer history.[Table: see text]

443 Background: Electronic cigarette smoking and similar novel smoking modalities have raised questions about their impact on various cancers compared with traditional forms of tobacco smoking. Tobacco smoking has been concretely proven to increase the risk of many cancers, including lung (LCa) and bladder (BCa) cancer. To date, there is little data on how e-cigarette smoking impacts the incidence of these cancers. We investigated whether any disparities exist in the prevalence of LCa and BCa between various smoking histories using a US nationally representative data source. Methods: This cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database between 2016-2018. Primary endpoint was self-reported occurrence of LCa and BCa diagnosis. Multivariable logistic regression analyses assessed possible association of various covariates with diagnosis of these cancers. Results: Prevalence of BCa and LCa was higher in all smoking histories compared to never smokers. Patients with a history of e-cigarette smoking vs. no history of e-cigarette smoking were significantly younger at BCa diagnosis (56.87 [±9.86] vs. 65.00 [±12.60] years, p=0.001). Multivariable logistic regression models showed that a history of cigarette smoking and e-cigarette smoking individually was associated with increased ORs of 2.476 (p≤0.001) and 1.577 (p≤0.001) for BCa diagnosis, respectively, and 4.589 (p≤0.001) and 1.614 (p=0.007) for LCa diagnosis, respectively. Conclusions: Compared to never smokers, history of e-cigarette smoking was associated with increased risk of LCa and BCa development and earlier BCa diagnosis. Additional studies are needed to better define the public health effects of these novel and unregulated products.

1525 Background: Studies show that cancer patients and survivors are likely to endure financial toxicity long after being diagnosed. Methods: To examine the influence of race on financial toxicity among individuals with a history of cancer, a US based cross sectional study was conducted using data on 1,328 cancer patients collected from the Health Information National Trends Survey. Multivariable logistic regression analyses were used to analyze the relationship between race and financial toxicity, adjusting for known confounders. Results: Blacks, Hispanics and other races were shown to have a lower rate of insurance compared to Whites. Whites were also more likely to receive cancer treatment than other races (6.1% received no treatment vs 15.0% of Blacks, 17.8% of Hispanics, and 9.7% of other races, p

229 Background: RTOG0521 and STAMPEDE showed improved Overall survival (OS) and progression free survival (PFS) respectively, of ACT (adjuvant chemotherapy) to ADT (androgen deprivation therapy) and RT (adjuvant radiotherapy) in HrPC (High Risk localized Prostate Cancer). The median age of males in these trials is in 60’s. We present an observational study reporting OS on addition of ACT to ADT and RT in male age > 65 with HrPC. Methods: A retrospective national cancer center database (NCDB) (2004-2015) analysis was done. Patients aged >65 years with non-metastatic HrPC who underwent ADT and RT with or without ACT were included. Group1 included RT+ ADT+ ACT, Group2 included RT+ ADT. OS was estimated using Kaplan Meier analysis, reported for sub groups based on age. An adjusted hazard ratio (aHR) was calculated utilizing a Cox proportional hazard regression model. Results: 1,380,357 patients with HrPC were identified. 11734 met our inclusion criteria; 128 in Group1 and 11606 in Group2. Median Age, Gleason and PSA were: Group1- 72, 9, 14.6, Group2- 74, 9 and 14. Patients who received ACT were more likely to be younger and treated in an academic setting. OS stratified by age is depicted in table. Among patients ≥ 75, OS was uniformly worse with ACT with non-significant p value (p=0.08). The aHR, group 1 vs group 2 is 1.22, 95% CI = 0.96-1.57, p=0.11, when adjusted for Age, Facility Type, Insurance, and Charlson-Deyo Score (CDS). Conclusions: Very elderly patients ≥75 years were not likely to get ACT. OS was not improved by addition of chemotherapy, at age ≥ 65yrs and more prominent at age ≥ 75. Limitations of observational database study are lack of randomizations, missing information, physician bias on choices of ACT, RT and ADT. [Table: see text]

Background Melanoma is among the top three cancers to present with brain metastasis. The risk of brain metastases in advanced melanoma increases with disease duration. Cytotoxic chemotherapy does not have a significant role in the management of melanoma patients with brain metastases, neither alone nor in conjunction with radiation therapy. Patients and methods We herein discuss a case of a 66-year-old male diagnosed initially with stage III-B melanoma and underwent a wide local excision with a split thickness graft and sentinel lymph node biopsy, followed by adjuvant treatment with high-dose interferon. Results On subsequent follow up he was found to have a brain lesion, which later on resolved after starting ipilumumab. Five to twenty percent of patients with melanoma of any stage develop cerebral metastases. Conclusion Immunotherapy modalities, ipilimumab has been shown to have activity against brain metastases.

Key Clinical Message Ascites with the finding of peritoneal carcinomatosis is considered an unusual presentation for mantle cell lymphoma (MCL) and has been rarely described in literature. This case reflects the importance of cytological analysis of peritoneal fluid in a patient with intractable ascites not contributing from other comorbidities. In the event a bone marrow (BM) analysis cannot be made, this may serve as an alternative method for diagnosing MCL taking into consideration the good concordance between peritoneal fluid and BM cytological markers.

3 Background: Scrotal squamous cell carcinoma (SSCC)thoughrare, represents the most common forms of scrotal malignancies.40-50% of patients present with locally advanced disease, and treatment is extrapolated from penile cancer. Here we report practice trend and overall survival (OS) outcome of locally advanced SSCC patients who underwent surgery with or without chemotherapy. Methods: We performed a retrospective analysis using the national cancer center database (NCDB) (2004-2016). All patients aged ≥ 18 years with locally advanced SSCC who underwent surgery with or without chemotherapy were included. OS is estimated with Kaplan-Meier curves, with an adjusted hazard ratio (aHR) calculated from Cox proportional hazard regression model. Results: 638 patients were identified with SSCC without distant metastasis. Of these 49 underwent surgery with perioperative chemotherapy and 589 underwent surgery alone. At the median follow up of 39.9 months (mo), median OS is 41.4 mo and 145.7 mo for surgery with chemotherapy group versus surgery alone respectively (P-value

Immunotherapies such as the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab and the programmed cell death protein 1 inhibitor nivolumab have become ubiquitous in cancer treatment. Recently, the FDA approved nivolumab with or without ipilimumab for the treatment of refractory small cell lung cancer. Immunotherapies increase the immune response to cancer cells by interfering with inhibitory molecular pathways that prevent tumor cell killing, thus augmenting tumor cell death without many of the cytotoxic side effects associated with chemotherapy. However, this augmented immune response may result in unwanted immune-mediated inflammation of different organs and are therefore associated with immune-related adverse events, unlike traditional chemotherapies or targeted therapies. Here, we describe 1 patient with advanced small cell lung cancer who developed grade III-IV acute inflammatory demyelinating polyradiculoneuropathy after treatment with ipilimumab and nivolumab. The patient was treated with intravenous immunoglobulin alone and showed symptomatic improvement.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid. Majority of the PTC carries an excellent prognosis. However, patients with tall cell variant (TCV) of papillary thyroid carcinoma have a worse prognosis than those with the classic variant. On the other hand, squamous cell carcinoma of the thyroid (SCT) is an unusual neoplasm thought to arise as a primary tumor or as a component of an anaplastic or undifferentiated carcinoma. We report a patient with TCV of PTC presenting years later with squamous transformation. In addition, the patient was found to have BRAF mutation. Such dedifferentiation is considered to be a rare phenomenon and has been reported only in the form of case reports in the literature. The relationship between BRAFV600E mutation and squamous cell transformation of papillary thyroid cancer is unknown at this time. Meticulous pathology is needed to identify such variants. Our patient responded to treatment with concurrent chemotherapy with carboplatin and paclitaxel along with radiation.

Adenocarcinoma is the most common type of non-small-cell lung cancer (NSCLC). Adenocarcinoma with epidermal growth factor receptor (EGFR) mutations accounts for 8%-30% of all cases of NSCLC depending on the geography and ethnicity. EGFR-mutated NSCLC usually responds to first-line therapy with EGFR tyrosine kinase inhibitors (TKIs). However, there is eventual loss of efficacy to TKIs due to development of resistance. The most frequent cause for resistance is a second EGFR mutation in exon 20 (T790M), which is encountered in up to 62% of patients. Osimertinib is one of the third-generation EGFR TKIs with a high selective potency against T790M mutants. In Phase I trial of osimertinib in advanced lung cancer after progression on EGFR TKIs, the response rate and disease control rate were 61% and 95%, respectively. A subsequent Phase II (AURA2) trial demonstrated a disease control rate of 92%, a response rate of 71%, a median duration of response of 7.8 months, and a median progression-free survival of 8.6 months. Osimertinib was approved by the US Food & Drug Administration in November 2015 for patients whose tumors exhibited T790M mutation and for those with progressive disease on other EGFR TKIs. In this review, we address the role of EGFR TKIs in the management of EGFR mutation lung cancer and the mechanisms of resistance to TKIs with a focus on the role of osimertinib. Data from completed trials of osimertinib, ongoing trials, as well as novel diagnostic methods to detect EGFR T790M mutation are reviewed.

Patient: Female, 31 Final Diagnosis: Hemophagocytic lymphohistiocytosis (LHL) Symptoms: Hemopthysis Medication: — Clinical Procedure: — Specialty: Oncology Objective: Rare disease Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome. HLH can occur in the setting of an autoimmune disease, chronic immunosuppression, malignancy, and infection. We discuss a rare case of a young woman who was diagnosed with Goodpasture’s syndrome that was most likely complicated by HLH. To the best of our knowledge, this is the first report of HLH in the setting of this rare autoimmune disease. Case Report: A 31-year-old woman who was diagnosed with Goodpasture’s syndrome 7 years prior presented with febrile neutropenia. She was initially receiving treatment with azathioprine and prednisone, which was subsequently switched to hydroxychloroquine. Over time, she had developed polyarthritis and was later diagnosed with MPO-ANCA-positive vasculitides. On this admission, her clinical status deteriorated from persistent pancytopenia. This was initially attributed to the immunosuppressive effect of hydroxychloroquine. A bone marrow biopsy was performed and revealed hypercellular bone marrow without any cytogenetic abnormalities. Due to a prolonged pancytopenia thought to be of autoimmune etiology, treatment with high-dose steroids was initiated. With the persistent febrile episodes, hepatosplenomegaly on examination, and laboratory workup that revealed hyperferritinemia and pancytopenia, HLH syndrome was suspected. A repeat bone marrow biopsy confirmed this diagnosis with the presence of hemophagocytosis, demonstrated by the presence of histiocytes engulfing erythroid cells. She also met 5 of 8 diagnostic criteria, which confirmed the diagnosis of HLH. The patient eventually died despite aggressive treatment with high-dose steroid therapy for her autoimmune disorder, as well intravenous antibiotics and supportive care for her underlying infections. Conclusions: HLH is a syndrome marked by a hyper-inflammatory state aggravated by specific triggers. To make the diagnosis of HLH, at least 5 of the 8 criteria must be met. Treatment involves suppression of the overwhelming inflammatory response by the use of immunomodulators. The mortality rate can range from 50–90% due to delayed recognition and onset of treatment. Here, we present a rare case of Goodpasture’s syndrome with overlap and pauci-immune vasculitis, which may have triggered the HLH. This correlation has not been described before in the literature.

Background: Diffuse large B cell lymphoma (DLBCL) NOS is the most common histologic subtype of non-Hodgkin lymphoma (NHL). Double hit lymphoma is re-classified as high-grade B cell lymphoma, with and without MYC and BCL2 or BCL6 rearrangements (HGBCL) in 2016. The International Prognostic Index (IPI) is the main prognostic tool for DLBCL NOS. We aimed to identify if IPI index scores can accurately predict the prognosis in patients with HGBCL. Methods: We observed the outcome of a cohort of patients (pts) with DLBCL NOS and HGBCL diagnosed and treated from 2008-2019 at SUNY Upstate Medical University. Fisher's exact test was used for the 2X2 comparison analysis. Results: 24 pts (82.8%) had DLBCL NOS and 5 (17.2%) pts had HGBCL. The median age was 58 yrs (13-81 yrs). 65.5% were males and 79.3% were caucasians. 8 pts had bone marrow involvement, 1 pt had brain metastasis and 12 pts had bulky disease. 15 DLBCL NOS pts (68.2%) and 4 HGBCL pts (80%) had low-intermediate IPI (/=4). 2 DLBCL NOS pts (13.33%) vs 1 HGBCL pt (25%) died in the low-intermediate IPI group. None of the DLBCL NOS pts (0%) vs 1 HGBCL pt (100%) died in the high risk group. Conclusion: Our study sample size is very small to identify prognostic relation of IPI score to predict the outcome for HGBCL. Our observation raises the hypothesis that patient with HGBCL might have a worse prognosis despite low IPI score which needs to be validated in a larger study population. Disclosures No relevant conflicts of interest to declare.

4533 Background: We performed a CGP to compare the genomic alterations (GA) in ABC, UBC and SCCB. Methods: 143 cases of ACB, 2,142 cases of UCB and 83 cases of SCCB were subjected to CGP using a hybrid-capture based assay. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by IHC. Results: ABC patients were younger and more often female than UBC and SCCB (P < 0.0001). UBC and SCCB had a higher GA/tumor than ABC (P = 0.01). Un-targetable GA were similar in all 3 groups involving TP53 and KRAS. APC GA were more frequent in ABC whereas TERT, CDKN2A/B and DNA-repair genes ( ARID1A and KDM6A) more frequently altered in UBC and SCCB. Targetable MTOR pathway GA ( PIK3CA, TSC1, PTEN) were more frequent in UBC and SCCB as were targetable kinase alterations ( FGFR3 and ERBB2). The UBC and SCCB had a significantly higher TMB than ABC (P < 0.0001) including mean TMB and TMB > 20 mut/Mb (P < 0.0001). CD274 (PD-L1) was amplified more frequently in SCCB than ACB or UBC (P < 0.0001). MSI high status was very uncommon in all tumor types. Conclusions: Deep sequencing reveals that ABC features a widely different genomic profile from UBC and SCCB. UBC has the highest frequencies of targetable kinase GA and high TMB. SCCB has the highest frequencies of IO efficacy predicting biomarkers including mean TMB and PD-L1 amp. Nonetheless, ABC does feature potential kinase targets such as FGFR3 and ERBB2. [Table: see text]

408 Background: Five year cancer specific survival rate is between 12- 70% for pT2 and higher UUTUC tumors. Adjuvant platinum based therapies have proven to improve Overall survival (OS) in observational series. Compromised renal function after surgery, delayed recovery from surgery pose challenge for adjuvant chemotherapy (AC). Thus, neoadjuvant chemotherapy (NAC) is an appealing option. However, there is only limited evidence on the role of NAC in UUTUC. Methods: We conducted a retrospective study of UUTUC (stage I- III) who underwent complete or partial nephroureterectomy with peri-operative chemotherapy. We then compared OS outcome among NAC vs AC groups. OS was calculated using Kaplan Meier analysis. Multivariate analysis was performed with Cox proportional hazard regression model to adjust for different variables. Results: Out of 50539 UUTUC patients reported in NCDB (2004-2016), 20121 met our inclusion criteria. 360 patients received NAC, 2617 received AC and 17144 received only surgery. Patients who received NAC were more likely to be younger, treated at academic centers, have Medicare and private insurance, have clinical T3 and higher tumor, have lower Charlson-Deyo Score (CDCC) score and undergo complete nephroureterctomy. One, three and five year OS among NAC and AC is depicted in table 1. With 150 months (m) follow up, median OS was 73.89 m for NAC and 54.14 m for AC group. A log rank test with p value=0.3437 shows no significant difference in survival rates of the two groups. Though consistent upward trend is observed in the use of NAC from 2004 to 2015, significantly higher percentages of patients still undergo only surgery without perioperative chemotherapy. Conclusions: Numerically higher mOS in NAC group was not statistically significant different from AC group. Use of perioperative chemotherapy appears to be much lower in UUTUC. Limitations that exist with this registry based study include lack of randomization, differences in surgical and radiation techniques, duration of chemotherapy, and provider/patient selection bias. Overall survival among two groups. [Table: see text]

118 Background: Phase III trials have not consistently demonstrated overall survival (OS) advantage of adjuvant radiation therapy (ART) in prostate cancer (PC) with high risk/very high risk features after radical prostatectomy (RP). Adjuvant hormone therapy (AHT) in PC after RP improved OS in patients with positive lymph nodes (pLNs). We report an observational study on the impact of AHT to ART in NCCN defined high-risk/very high risk (Group 1), and adjuvant chemotherapy (ACT) to AHT in pLNs (group 2) post RP on OS. Methods: We conducted a retrospective study of PC patients (group 1 and group 2) who underwent RP and/or pelvic lymph node dissection. OS was calculated using Kaplan Meier analysis. Group 1 compared ART+AHT vs ART and Group 2 AHT+ ACT vs AHT within 16 weeks of RP. Multivariate analysis was performed with Cox proportional hazard regression model to adjust for different variables. Results: Out of 1,390,357 PC patients reported in NCDB (2004-2015) 182,653 and 11,972 met our inclusion criteria for Group 1 and Group 2 respectively. 3.37% of Group 1 received ART and/or AHT. 19.81% of Group 2 received AHT and/or ACT. Patients who received ART + AHT were more likely to be older, Non-Hispanic white, more likely to have pT4, and have higher prostate specific antigen (PSA) and Gleason scores (GS). Patients who received AHT+ACT were more likely to be younger, with private insurance, and lower Charlson-Deyo Score (CDCC) score. Five and seven year OS with adjusted hazard ratio (aHR) among Group 1 and Group 2 are depicted in table. Conclusions: No statistically significant difference in OS was seen among respective treatment groups. Limitations that exist with this registry based study include lack of randomization, differences in surgical and radiation techniques, duration and choices of ACT and AHT.[Table: see text]

Differences in microRNA (miR) expression levels provide clues to the disruption of normal hematopoiesis that leads to the emergence of a leukemic clone. Analysis of miR expression levels may be useful to understanding normal cytogenetic acute myeloid leukemias (AMLs) and developing novel treatments for them. We collected peripheral blood samples from 10 adult patients with newly diagnosed AML, prior to induction chemotherapy, and 9 controls. Two and a half ml of whole blood was collected in Paxgene RNA tubes. miRNA was purified using standard Trizol method, followed by RNeasy mini column (Qiagen). Quality of the RNA samples was assessed using the Agilent Bioanalyzer prior to library construction using the Illumina TruSeq Small RNA Sample Prep protocol (Illumina; San Diego, CA). Multiplexed samples of RNA that exceeded quality control metrics (RIN &gt 6.0) were run on an Illumina NextSeq500 instrument at a targeted depth of 10 million reads per sample. After filtering and trimming of index and adapter sequences, whole genome alignment of the miR FASTQ reads was performed using the Homo sapiens/hg19 reference genome in the SHRiMPS aligner included in the miRNAs analysis application available in BaseSpace (Illumina), as well as the sRNA Toolbox application suite. Quantification and normalization of aligned reads to the miRBase 21 database was performed, and differential expression between AML and control groups was performed using DESeq2, NOIseq, and EdgeR algorithms. We sequenced approximately 800 miRs from each of 10 patients with AML and 9 controls. We identified 9 miRs that showed a statistically significant increase in expression in AML patients versus controls and 4 miRs that showed a statistically significant decrease in expression in AML patients versus controls, with adjusted p-value less than 0.05. Among these 13 differentially expressed miRs, only 4 were previously described in leukemia, including miR 181a-3p and 181a-2-3p, miR 409-3p, and miR 126-5p. Finding these 4 miRs differentially expressed confirmed the validity of our approach. The remaining 9 of the miRs that showed differential expression in our study have not been described in relation to AML (miR-328-3p, miR106b-3p, let-7i-5p, miR10b-5p, miR-24-3p, miR-3200-5p, miR-23a-3p, miR-323b-3p, miR-652-3p). In subset analysis, patients with NPM1 and FLT3 mutations showed lower levels of miR 181a-2-3p and higher levels of miR 10b-5p compared to patients without NPM1 and FLT3 mutations. We are continuing to accrue patients to this study and we are following them over time in order to analyze miR expression in peripheral blood as a biomarker that may predict relapse. Our approach of global sequencing of miRs as opposed to microarray analysis removes the bias regarding which miRs to assay and has demonstrated discovery of new associations of miRs with AML. Our study provides further information about the molecular changes that lead to evolution of the leukemic clone and offers new targets for development of treatments. Citation Format: Diana Gilligan, Aakriti Pandita, Poornima Ramadas, Aarati Poudel, Nibal Saad, Ankit Anand, Alina Basnet, Frank Middleton. MicroRNA profiling in AML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5413.

5061Background: We hypothesized that sub-categorization of TMPRSS2 fusion status would impact therapy opportunities in patients with clinically advanced CRPC and CRNEPC. Methods: CGP was performed ...

e21586Background: Time delay from diagnosis to definitive surgery has negative impact on the overall and disease-specific survival in breast cancer but the same has not been proven for colon cancer...

Malignant triton tumors (MTTs) are rare and aggressive sarcomas categorized as a subgroup of malignant peripheral nerve sheath tumors (MPNSTs). MTTs arise from Schwann cells of peripheral nerves or existing neurofibromas and have elements of rhabdomyoblastic differentiation. We report the occurrence of MTTs in two sisters. The first patient is a 36-year-old female who presented with left sided chest wall swelling. She also had clinical features consistent with neurofibromatosis type 1 (NF-1). Debulking of the mass showed high-grade malignant peripheral nerve sheath tumor with skeletal muscle differentiation (MTT). The patient was treated with ifosfamide and adriamycin along with radiation. Four years after treatment, she still has no evidence of disease recurrence. Her sister subsequently presented to us at the age of 42 with left sided lateral chest wall pain. Imaging showed a multicompartmental retroperitoneal cystic mass with left psoas involvement. The tumor was resected and, similarly to her sister, it showed high-grade malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation (MTT). The patient was started on chemotherapy and radiation as described above.

17 Background: Despite ASCO’s recommendation to introduce palliative care services for all patients diagnosed with localized or metastatic pancreatic cancer, most patients’ care does not involve this multimodality approach. Transitioning patients to hospice at an appropriate time is essential in oncologic practice. The purpose of this study is to identify which variables affect acceptance of hospice services by patients. Methods: A retrospective chart review of patients with pancreatic cancer treated at Upstate University Hospital from 2011-2015 was performed. We studied variables including age, sex, race, stage, insurance status, advance directives, performance status and laboratory values. We analyzed patients based on acceptance or rejection of hospice care in their disease course and conducted a univariate analysis on different factors to determine predisposing variables. p-values were calculated using Chi-Square test and t-test. Results: We reviewed 325 patients charts and found statistically significant relation to acceptance of hospice and insurance status, and involvement of palliative care in their care. Patients with Medicare were more likely to decline hospice care whereas patients with Medicaid or no insurance were more likely to accept it. 36.23% of patients saw palliative care services at any point in their treatment course and these patients were more likely to accept hospice care than patients who did not (p = < 0.0001). Patients who were seen by palliative care earlier in their disease course were more likely to accept hospice care, although this did not reach statistical significance (p = 0.0731). Patients with stage IV disease were more likely to accept hospice care (p = 0.0095). Other variables like presence of advanced directives, tumor markers, age, and sex did not have a significant impact. Conclusions: Palliative care involvement is beneficial in patients with pancreatic cancer as they face a rough disease course with multiple treatment and disease related morbidities. Patients with early palliative care involvement during their illness are more likely to decide on hospice care at the end stages of their malignancies. This supports early palliative care introduction as an adjunct to oncologic care.

153 Background: Five year overall survival rate for localized and metastatic pancreatic adenocarcinoma (PAC) is discouraging at 31.5% and 2.7%, respectively. Evidence supports that early palliative care (PC) involvement leads to better quality of life and prolongs OS. Referral to PC is often delayed as it is perceived as an alternative rather than adjunctive care. We conducted a retrospective study to identify different variables that affect PC consultation among patients (pts) with PAC admitted to the hospital and to study the impact of health care utilizations on OS. Methods: A retrospective medical record review of pts with PAC diagnosed/treated at SUNY Upstate University hospital was conducted (2011-2015). Variables like age, sex, race, stage at diagnosis, insurance status, performance status (PS), frequency of hospital admissions, nights spent, procedure visits, blood products used, and time variable to PC referral from diagnosis were collected. OS was calculated using Kaplan Meier analysis. Results: We identified 325 pts with diagnosis of PAC. 86.72% pts had one or more hospital admissions during course of their illness and of these, 15.85% saw PC during initial inpatient admission. 36.23% saw PC later in the course of their illness and 13.96% pts were offered palliative care in first outpatient visit. Median time interval to see palliative care was 75 days (d) from diagnosis, with 25% pts seeing PC 304d from diagnosis. Variables that had significant impact on early palliative care encounter (0-30d) were age > 70, stage IV at diagnosis, PS of 4, medicare insurance, offered PC in first visit (p< 0.001). OS was not statistically significant between groups who had ≥ 1 vs 0 blood products given, < 3 vs ≥ 3 hospital admissions, ≤ 13 vs > 13 nights spent, ≥ 1 vs 0 procedures done, ≤ 3 vs > 3 consults service seen. Median OS for pts with time interval to see PC 0-30d vs > 120d was 33d and 510d respectively with adjusted hazard ratio of 6.252 (95% CI 3.462-11.29). Conclusions: We demonstrated that PC is underutilized with only minority of pts benefiting from it during their cancer treatment. OS was poor in group evaluated by palliative care early than late which could be due to patients with advanced disease and poor PS being referred early.

578 Background: Three small prospective trials that compared the efficacy of neoadjuvant endocrine therapy (NET) to neoadjuvant chemotherapy (NCT) showed no statistically significant difference. We report the differences in utilization of NET and NCT using National Cancer Data Base (NCDB) and their trend, response rates (RR) and breast conservation rates (BCR). Methods: A retrospective review of hormone receptor positive breast cancer patients ≥ 50 yrs without metastasis using NCDB was performed (2004-2014). Patients underwent NET or NCT prior to definitive surgery. Utilization pattern, practice trend, RR and BCR between NET and NCT was assessed using univariate and multivariate logistic analysis. Results: Out of 2,246,279 breast cancer patients reported in NCDB, 38,632 met our inclusion criteria. 9178 received NET and 29,454 received NCT. On multivariate analysis NET use was higher in academic vs community centers [Odds ratio (OR) 1.355, 95% CI 1.270-1.445], age >70 vs < 70 (OR 6.603, 95% CI 6.110-7.137) and high vs low Charlson Deyo comorbidity index (OR 1.817, 95% CI 1.548-2.133). NET use was lower in black vs white (OR 0.790, 95% CI 0.712- 0.875), tumors with higher vs lower grade (OR 0.153, 95% CI 0.138-0.169), higher vs lower T stage (OR 0.372, 95% CI 0.340-0.407), higher vs lower N stage (OR 0.274, 95% CI 0.243-0.310) and private vs no insurance (OR 0.600, 95% CI 0.509- 0.707), (all p

e12119 Background: Neoadjuvant endocrine therapy (NET) and neoadjuvant chemotherapy (NCT) are both considered effective strategies in postmenopausal, hormone receptor positive breast cancer patients. Small prospective studies show comparable response rates and breast conservation rates. Using National Cancer Data Base (NCDB) we report overall survival (OS) differences between these two strategies with subgroup analysis by Estrogen Receptor (ER), Progesterone Receptor (PgR) status. Methods: We extracted data on hormone receptor positive breast cancer patients without metastasis in women aged ≥ 50 from the NCDB registry (2004-2014). We excluded patients who did not receive adjuvant endocrine therapy after NCT and patients who received adjuvant chemotherapy after NET as this could affect OS. We calculated OS using Kaplan Meier analysis with hazard ratio (HR) from cox regression model. Subgroup analysis was performed by ER, PgR status. Results: Out of 2,246,279 patients, 30,348 patients met our inclusion criteria. 7836 received NET and 22512 received NCT. OS rate was 70.8% vs 81.7% at 5 yrs and 42.5% vs 62.1% at 9 yrs for NET and NCT respectively with adjusted hazard ratio (HR) of 1.818; 95% CI (1.657-1.996). OS outcome for ER+/PgR+ group was 72.3% vs 83.5% at 5 yrs and 43.5% vs 64% at 9 yrs for NET and NCT respectively with adjusted HR of 1.807; 95% CI (1.624-2.010). OS for ER+/pgR- group was 62.9% vs 76.8% at 5 yrs and 33.1% vs 54.2% at 9 yrs for NET and NCT respectively with adjusted HR of 1.890; 95% CI (1.549-2.306). Our analysis also revealed that 5591 T1 patients received neoadjuvant therapy among which 2541 received NET and 3050 received NCT. Conclusions: We find a significant survival advantage in patients treated with NCT as opposed to NET. All subgroups showed imporved OS with NCT compared with NET. Limitations that should be considered in this registry based study are: not accounting for Her-2 status, differences in surgical technique, duration and choices of adjuvant chemotherapy and radiotherapy options.