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Plain language summary Targeted immunotherapy refers to a new class of drugs that boost the body's immune system to fight against cancer. Studies have shown that immunotherapy increases the survival of kidney cancer patients, but it has certain side effects that can affect any organ in the body, including the heart, lungs, skin, bowel and thyroid. Most side effects can be managed with drugs that can suppress the immune system, such as steroids; however, some side effects can be fatal if not diagnosed in a timely manner. It is vital to have a proper understanding of the side effects of immunotherapy drugs when making decisions about treatment for kidney cancer.

Introduction: Metabolic reprogramming is recognized as a hallmark of malignancy. Cancer growth, and progression has been associated with lipid and amino acid absorption by cancer cells. However, the differential impact of chemotherapeutic agents on energy balance and metabolism while on-treatment and at the time of clinical progression, in breast cancer patients, is largely unknown. We hypothesize that increases in lipid and other related metabolites, like amino acids, throughout chemotherapy treatment are therapy-specific, and associated with disease progression. Methods: Serum samples from 15 metastatic breast cancer patients (hormone-receptor positive and triple negative breast cancer), receiving different chemotherapy regimens (n=5 paclitaxel, n=5 eribulin, n=5 capecitabine), were collected at multiple time points (baseline, 3- week on-treatment and disease progression). Disease progression was determined by CT scans using RECIST v1.1 criteria. Samples were prepared for metabolomics and analyzed via mass spectrometry using the MxP Quant 500 kit (Biocrates Life Sciences AG, Innsbruck, Austria). Data was processed using MetIDQ software (Biocrates Life Sciences AG). Limma was used to identify differential metabolites during treatment and at the time of disease progression as compared to metabolites at baseline. Results: With capecitabine treatment, there was a differential impact on many lipid metabolites, including ceramides, with an initial decrease on treatment: Cer(d18:2/18:1)(-1.95 log-fold change (logFC)); and arachidonic acid, (-1.32 logFC) (p< 0.05 for both). However, at the time of disease progression, there was a 1.8 to 2 log-fold increase in Cer (d18:0/20:0); Cer (d18:1/22:0); Cer (d18:2/22:0); Cer (d18:1/23:0); 1.7 log-fold increase in diacylglycerol (DG (16:0_20:0)) along with 1.6 log-fold increase in amino acid methionine (p < 0.05 for all). Conversely, in the eribulin group, while on treatment, there was a 1.2 to 1.3 log-fold increase in triglycerides (TG), i.e., TG(16:1_36:2); TG(16:0_36:2); TG(18:1_33:1); TG(16:1_36:1); TG(20:4_34:1) and 1.5 log-fold increase in amino acid kynurenine; while there was a 1.3 to 1.4 log-fold decrease in fatty acids (FA), such as FA(20:2); FA(18:2); FA(18:1) (p < 0.05 for all). At the time of disease progression, there was a 1.2 to 1.3 log-fold decrease in lipids like cholesteryl esters (CE) and phosphatidylcholines (PC), e.g. CE (18:2); CE (18:3); PC aa 36:3; PC aa 36:2 (p < 0.05 for all). Similarly, in the paclitaxel group, with treatment, there was a 1.2 to 1.8 log-fold increase in CE(22:0); Hex2Cer(d18:1/26:1) and DG(18:3_20:2) (p < 0.05 for all), while, at the time of disease progression, there was a 2 log fold decrease in PC like lyso PC a C20:3; and lyso PC a C16:1, as well as 2 to 2.5 log-fold decrease in amino acids like glutamine, and sarcosine (p < 0.05 for all). Conclusion: Lipid and amino acid pool while on treatment and at disease progression were differentially impacted by the three classes of chemotherapies, some of which to the same functional extent. Although a decrease in lipid metabolites was observed while on capecitabine (prodrug of 5-fluorouracil) treatment, an increase in both lipid metabolites and amino acids was observed at disease progression. With both paclitaxel and eribulin treatment, which are microtubule inhibitors, a decrease in lipid metabolites and amino acids was observed at disease progression. An understanding of differential metabolic reprogramming with different chemotherapeutic agents may provide novel points of therapeutic intervention for anti-cancer treatment, such as combination of chemotherapy with inhibitors of ceramide metabolism or amino acid inhibitors and contribute towards efficacious personalized medicine. Citation Format: Shipra Gandhi, Arya Mariam Roy, Kazuaki Takabe, Spencer Rosario. Capecitabine, eribulin and paclitaxel differentially impact the metabolite pool in metastatic breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-11-06.

Background: Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced breast cancer (BC). Patients (pts) who attained pathological complete response (pCR) with NAC have a better prognosis when compared to those who have residual disease (RD). We analyzed the association of race with neoadjuvant chemosensitivity in early BC and the overall survival (OS) based on the chemosensitivity. Methods: We queried the National Cancer Database for early BC pts who received NAC from 2010-2016. Preoperative chemosensitivity was defined as very sensitive (VS) (ypT0/TisN0), sensitive (S) (pathological TNM stage less than clinical, excluding ypT0N0), and refractory (R) (pathological greater than or equal to clinical). Demographic, clinical, treatment, and survival rates were summarized by race focusing on neoadjuvant chemosensitivity. All associations were compared using Kruskal-Wallis, Pearson’s Chi-Squared, and Fisher’s Exact Tests. Multivariate cox models were generated for the OS. All analyses were conducted in RStudio v4.0.2 at a significance level of 0.05. Results: A total of 103,605 pts who received NAC were analyzed. 43.2% (n= 44,796) were R, 34.4% (n= 35,638) were S and 22.4% (n= 23,171) pts were VS. The 3-year (yr) OS rates for R, S, VS groups were 81%, 88%, 95% respectively (rsp) (p< 0.001). The 5-yr OS rates were 73%, 82%, 92% rsp (p < 0.001). In the hormone-receptor positive HER2 negative (HR+) subtype, only 8.9% (n= 3,837) were VS, while among triple negative breast cancer (TNBC) subtype, 28.4% (n= 9,224) pts were VS, among HER2 positive (HER2+) subtype, 36.7% (n=9,665) pts were VS and in both subtypes around 28-36% were R as opposed to 58.4% with R disease among HR+ subtype. Among HR+ group, pts had more R disease regardless of race (all races R: 54-57%, p < 0.001). Among HER2+ disease, Blacks had lower percentage of VS disease compared to other races (32% vs 37-40%, p< 0.001). Among TNBC, more R disease was seen among Blacks compared to other races (38% vs 30-35%, p< 0.001). In whole cohort, as expected, compared to pts with R disease, pts with S and VS disease had lower overall mortality risk (HR= 0.45, 95% CI= 0.43 – 0.46, P< 0.001, HR= 0.20, 95% CI = 0.19- 0.21, p < 0.001 rsp). In TNBC subgroup among pts with R disease, the median OS of Blacks was significantly lower compared to whites (71.9 vs 101.8 months, p < 0.001). Among BC subtypes, the 3-yr and 5-yr OS for R (65%, 56%) and S groups (83%, 76%) were significantly lower in TNBC when compared to other subtypes (HR+ R: 3-yr- 88%, 5-yr- 79% and S: 3-yr- 90%, 5-yr- 83%; HER2+ R: 3-yr- 85%, 5-yr- 77% and S: 3-yr- 92%, 5-yr- 86%, p< 0.001). In the whole cohort, Blacks with R, S, VS disease had significantly lower 3yr (73%, 85%, 94% rsp) and 5yr OS (63%, 78%, 91% rsp) compared to all other races and this was more prominent in the R and S groups (Table 1). Conclusion: Blacks diagnosed with TNBC were more resistant while other races were more sensitive to NAC. In all BC subtypes, Blacks had lower 3-yr and 5-yr OS regardless of chemosensitivity (including those who attained pCR), though this disparity was more predominant among those with residual disease after NAC (resistant and sensitive group). Since Blacks who do not attain pCR have worse survival compared to other races, it highlights the need to design more effective and personalized treatment strategies for Blacks to help them attain pCR, especially in the TNBC subtype. Table 1: Racial Disparities in Survival in Different Chemosensitivity Groups Citation Format: Arya Mariam Roy, Kayla Catalfamo, Kristopher Attwood, Shipra Gandhi. Racial disparities in neoadjuvant chemosensitivity and survival in early breast cancer: A national database study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD1-07.

Introduction: Socioeconomic status (SES) of the individual and neighborhood plays an important role in patients’ (pts) access to the health system and eventually in the outcomes of their disease. Owing to the inequalities in opportunities, education, income, and developmental infrastructures, the area with deprived individual and neighborhood SES may be associated with a poor prognosis of certain malignancies and worse outcomes. We analyzed the association between Neighborhood Deprivation Index (NDI) and survival of early-stage breast cancer (BC). Methods: The NDI created by the National Cancer Institute includes variables from dimensions, such as, wealth and income, education, occupation, and housing conditions which have been used for our analysis. We analyzed the impact of NDI in quintiles (qn). We queried the SEER database from 2010-2016 for all early-stage BC pts and studied the overall survival (OS) and disease-specific survival (DSS) of BC in association with NDI. Cox multivariate regression modeling was performed to measure the association between NDI and OS/DSS. Kruskal-Wallis test was used for comparison for continuous and Chi-Square test was used for categorical variables. All analyses were adjusted for age, race, grade, insurance, surgery (SX), radiation (RN), and chemotherapy (CT). Statistics were performed using SAS. Results: Out of the 88,572 early-stage BC pts, 27.4 % (n= 24,307) were in the most deprivation (MD) qn, 26.5% (n= 23,447) were in the average deprivation (AD) qn, 17% (n= 15,035) were in the above average deprivation (AA) qn, 15.6% (n= 13,838) were in the least deprivation (LD) qn and 13.5% (n= 11,945) were in the below average deprivation (BA) qn. The median age of pts in the LD qn was 59 and MD qn was 61 yrs, p< 0.001. There was a predominance of racial minorities in the MD and AA qn with Blacks being 13-15% and Hispanics being 15% compared to only 8% Blacks and 6% Hispanics in the LD qn (p< 0.001). There was a higher percentage of uninsured pts in the MD qn compared to LD qn (2.2% vs 1.7%, p< 0.001). There were more rural areas in MD qn compared to LD qn (25.9% vs only 0.7%, p< 0.001). There were more pts with grade III disease in MD qn compared to LD qn (34% vs 31.9%, p< 0.001). 96.1% pts underwent SX in MD qn vs 97.1 % had SX in LD qn, p< 0.001. Similarly, 49.7% underwent RN in MD qn vs 56.5% had RN in the LD qn, p< 0.001. Greater percentage of pts received CT in MD qn compared to LD qn (44.6% vs 42.1%, p< 0.001). There was a higher percentage of more aggressive cancers such as triple-negative breast cancer (TNBC) and HER2 positive (HER2+) in MD qn compared to LD qn (14.5%, 17.7% vs 11.7%, 16.5% respectively, p< 0.001). In multivariate analysis, in the overall cohort, those who live in AA qn and MD qn have inferior OS and DSS when compared to those who live in LD qn (OS in AA: Hazard Ratio (HR) 1.3, 95% CI: 1.2-1.4; OS in MD: HR 1.2, 95% CI: 1.1-1.3; DSS in AA: HR 1.3, 95% CI: 1.2-1.5; DSS in MD: HR 1.2, 95% CI: 1.1-1.4, all p< 0.001). Similar results in OS and DSS were observed in hormone receptor-positive HER2 negative (HR+) and HER2+ subtypes, but not in TNBC (Table 1). The 5-year OS rates and DSS rates were also comparatively low in AA qn and MD qn compared to LD qn (OS: AA- 84%, MD- 85%, LD- 98%; DSS: AA- 91%, MD- 92%, LD- 95%, all p< 0.001). Conclusion: Early-stage BC pts from areas with worse NDI have poor OS and DSS, after accounting for the demographic, clinicopathological, treatment-related factors. Investments in poor-resource neighborhoods and policies focusing on improving the SES of areas with high deprivation need to be implemented to reduce health care disparities and improve breast cancer outcomes. Table: Overall Survival and Disease Specific Survival Citation Format: Arya Mariam Roy, Anthony George, Kristopher Attwood, Shipra Gandhi. Neighborhood Deprivation Index and Survival in Breast Cancer in the United States [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD1-04.

Purpose To analyze the association between the Neighborhood Deprivation Index (NDI) and clinical outcomes of early-stage breast cancer (BC). Methods Surveillance, Epidemiology and End Results (SEER) database is queried to evaluate overall survival (OS) and disease-specific survival (DSS) of early- stage BC patients diagnosed between 2010–2016. Cox multivariate regression was performed to measure the association between NDI (Quintiles corresponding to most deprivation (Q1), above average deprivation (Q2), average deprivation (Q3), below average deprivation (Q4), least deprivation (Q5)) and OS/DSS. Results Of the 88,572 early-stage BC patients, 27.4% (n = 24,307) were in the Q1 quintile, 26.5% (n = 23,447) were in the Q3 quintile, 17% (n = 15,035) were in the Q2 quintile, 13.5% (n = 11,945) were in the Q4 quintile, and 15.6% (n = 13,838) were in the Q5 quintile. There was a predominance of racial minorities in the Q1 and Q2 quintiles with Black women being 13–15% and Hispanic women being 15% compared to only 8% Black women and 6% Hispanic women in the Q5 quintile (p

Background: Experimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate with an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates have higher odds of achieving pathologic complete response (pCR) and better survival outcomes than patients living in colder climates. Methods: A retrospective population-based analysis was conducted on Stage I-III breast cancer patients utilizing data from National Cancer Database (NCDB) from 2010-2018 with 892,092 patients and Surveillance, Epidemiology and End Results (SEER) from 1996-2017 with 270,496 patients. The average annual temperature (AAT) was calculated based on data from the National Centers for Environmental Information. Results: In the SEER cohort, patients residing at AAT ≥47.5°F had a 16% higher overall survival (OS) (HR 0.84, 95% CI 0.81- 0.88, p Conclusions: Higher environmental temperatures are associated with significantly better OS and DSS, as well as higher odds of achieving pCR in these patients. Future research is warranted to confirm this observation using large datasets, to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes.

INTRODUCTION: Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against clotting factor VIII. It occurs most commonly in the elderly population. AHA is associated with malignancy, autoimmune diseases, pregnancy, and drugs. However, up to 50% of reported cases remain idiopathic. AHA is very rarely associated with multiple sclerosis. CASE PRESENTATION: A 56-year-old patient with a history of MS presented with thigh and arm swelling and associated pain. Imaging revealed diffuse iliopsoas hematoma. Laboratory studies showed that prothombin time was not elevated and there was prolongation of activated partial thromboplastin time that was not corrected by mixing studies. Clotting factor VIII activity level was reduced, and the inhibitor level was elevated. He was treated with factor eight inhibitor bypassing agents, rituximab, and steroids. CONCLUSION: AHA should be suspected in any patient with new-onset bleeding in the presence of a prolonged activated partial thromboplastin time. Prompt diagnosis and treatment are important as AHA carries a high mortality rate.

Purpose Protein homeostasis regulated by the Endoplasmic Reticulum (ER) is a recognized process involved in cancer progression. ER stress activates the Unfolded Protein Response (UPR) and has been implicated in a variety of cancers. Given the role of the UPR activation in carcinogenesis, we hypothesized that UPR activation could be associated with pathological progression, higher clinical stage, and worse survival in breast cancer. Methods A total of 4,416 breast cancer patients from multiple independent cohorts were analyzed. We defined the UPR pathway score by the degree of enrichment by Gene Set Variant Analysis and median was used to divide high vs low score groups in each cohort. Results High UPR breast cancer significantly enriched not only cell proliferation-related but also other pro-cancerous gene sets consistently in both METABIC and GSE96058 cohort. Majority of UPR pathway score high cells in the bulk tumor were tumor cells compared to other cells, including stromal, T-, B-, and myeloid-cells (p p p p p = 0.041). Conclusion UPR signaling is associated with cancer aggressiveness, and worse survival, especially ER-positive/HER2-negative breast cancer subtype.

Introduction: Breast cancer (BC) is a heterogenous disease with multiple histological variants (HV) differing in their aggressiveness, survival, and response to treatments. Given the rarity of the HVs, very little is known about their treatment and chemosensitivity. The benefit of chemotherapy (CT) is unclear in hormone receptor-positive HER2 negative (HR+) subtype in the mucinous, medullary, cribriform, and papillary HVs in the NCCN guidelines. We aim to study the benefit of CT in these BC histologies. Method: We queried the SEER database from 2010-2018 for stage I, II, and III HR+ BC patients (pts) with mucinous, medullary, cribriform, and papillary histologies and examined their overall survival (OS) and disease-specific survival (DSS). Pts with metastatic disease and carcinoma in situ were excluded. The population was divided into two cohorts based on the receipt of adjuvant CT (CT positive (CT+) and CT negative (CT-) groups (gps)). Mann Whitney U and Fisher’s Exact test were used to compare continuous and categorical variables, respectively. Multivariate cox regression models were used for studying the association of CT with OS and DSS, controlling for confounding variables such as surgery, radiation, stage, grade, race, age, sex, and lymph node status. All analyses were conducted in RStudio v4.0.2 at a significance level of 0.05. Results: In the mucinous histology, out of a total of 11,745 pts, 94% (n= 6,788) were HR+. Among them, 8.5% (n= 580) were CT+ and 91.5% (n= 6208) were CT-. The 5-year (yr) OS was higher for CT+ compared to CT- among all stages (Stage I: 99% vs 92%, HR= 0.12; II: 96% vs 84%, HR= 0.22; III: 94% vs 40%, HR= 0.08, all p In the medullary histology, out of a total of 1,787 pts, 34% (n= 265) were HR+. Among these HR+ BC, all stage III pts received CT and their 5-yr OS was 94%. In stages I and II, CT+ had better 5-yr OS compared to CT- gp, (stage I: 99% vs 90%, p= 0.03, HR= 0.12, p= 0.07; II: 96% vs 91%, p= 0.03, HR= 0.23, p= 0.05). No 5-yr DSS benefit with CT was observed in any stage. Out of the total 1,110 BC pts with cribriform histology, 93% (n= 617) were HR+. Among them, 13.2% (n= 82) were CT+. The 5-yr OS was higher in CT+ compared to CT- in stage II (98% vs 82%, p=0.02, HR= 0.2, p= 0.036), but not in stage I or III. 5-yr DSS was not significantly better with CT in any stage. In the papillary histology, out of the total 1,698 pts, 83% (n= 889) were HR+. Among them, CT+ had better 5-yr OS compared to CT- only in stage II (86% vs 78%, p= 0.04, HR= 0.46, p= 0.047). There was no statistically significant DSS benefit with CT at any stage. Conclusion: In this large retrospective study, we observed that in mucinous and medullary histologies, adjuvant CT has OS benefit in HR+ BC subtype. In HR+ papillary and cribriform histologies, CT can be considered in higher stages. Multicenter clinical trials would be beneficial to assess the impact of CT in HVs and to formulate guidelines. Citation Format: Arya Mariam Roy, Syed Maaz Abdullah, Kayla Catalfamo, Kristopher Attwood, Shipra Gandhi. Benefit of chemotherapy in early-stage breast cancer with variant histology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 919.

Nephrectomy is the reference-standard treatment for renal-cell carcinoma (RCC). For patients with unresectable disease, tumor may be shrunk by using chemotherapy, thereby permitting surgical resection, which can be curative. We provided neoadjuvant cabozantinib, the preferred tyrosine kinase inhibitor for advanced RCC of poor and intermediate risk, to two patients with initially unresectable RCCs. In both patients, this led to tumor shrinkage of > 50% after 4 months of therapy, which permitted surgical resection. Both tumor specimens also showed strong pathologic tumor response. The robust responses observed with cabozantinib, even at reduced doses, suggest it to be an effective neoadjuvant option in RCC. Our novel experience with neoadjuvant cabozantinib, combined with our review of the use of cabozantinib in RCC, indicates that providing preoperative cabozantinib to facilitate potentially curative surgical resection has good results and should be further explored.

Therapeutic advancements in neuroendocrine tumors (NETs) have improved survival outcomes. This study aims to review the impact of the current therapeutics on health-related quality of life (HRQoL) in NET patients. A literature review was performed utilizing PubMed, The Cochrane Library, and EMBASE, using the keywords “Carcinoid”, “Neuroendocrine tumor”, “NET”, “Quality of life”, “Chemotherapy”, “Chemoembolization”, “Radiofrequency ablation”, “Peptide receptor radionucleotide therapy”, “PRRT”, “Surgery”, “Everolimus”, “Octreotide”, “Lanreotide”, “Sunitinib”, and “Somatostatin analog”. Letters, editorials, narrative reviews, case reports, and studies not in English were excluded. Out of 2375 publications, 61 studies met our inclusion criteria. The commonly used instruments were EORTC QLQ-C30, FACT G, and EORTC- QLQ GI.NET-21. HRQoL was assessed in all pivotal trials that led to approvals of systemic therapies. All systemic therapies showed no worsening in HRQoL. The NETTER-1 study was the only study to show a statistically significant improvement in HRQoL in several domains. The trial examining sunitinib versus placebo in pancreatic NETs showed no change in QoL, except for worsening of diarrhea. In addition to clinical outcomes, patient-reported outcomes are a key element in making appropriate treatment decisions. HRQoL data should be readily provided to patients to assist in shared decision-making.

476 Background: Small cell bladder cancer is a rare and aggressive histological variant with a paucity of data to guide the optimal management strategy in non-metastatic disease. NAC-RC and TMT (maximal transurethral resection of bladder tumor + chemoradiation) have been variably employed based on institutional preferences, and we aim to compare outcomes between these two approaches. Methods: We queried the National Cancer Database for adult patients with small cell bladder cancer diagnosed during the years 2004 to 2018. Patients with small cell histology and early-stage clinically node-negative bladder cancer (cT1-4N0M0) were included and divided into two groups based on the treatment strategy employed – NAC-RC or TMT. Patients who did not receive any definitive local therapy and those who received chemotherapy or radiation in the adjuvant setting were excluded. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 1262 patients were identified – 629 (49.8%) underwent NAC-RC while 633 (50.2%) received TMT. Patients in the NAC-RC group were younger (median 67 vs. 74 years, P

530 Background: Sarcomatoid bladder cancer is an extremely rare and aggressive histological variant with poor prognosis and limited consensus regarding its management given rarity and lack of high-quality data. Radical cystectomy (RC) is the mainstay of treatment in muscle-invasive disease and adjuvant therapy is often offered to eligible patients with high-risk features. Data regarding the role of neoadjuvant chemotherapy (NAC) for this variant is limited. Methods: The National Cancer Database was queried to identify patients diagnosed with sarcomatoid bladder cancer from 2004 to 2018. Patients older than 18 years with cT2-4aN0-1M0 sarcomatoid bladder cancer who received curative-intent surgery were included in the analyses. Clinical T4b/N2-3/M1 disease and receipt of adjuvant chemotherapy were employed as exclusion criteria. The population was divided into two cohorts based on the receipt of NAC. Chi-Square and Mann Whitney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed to adjust for confounding factors associated with overall survival. Models were adjusted for age, race, sex, income, stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 573 patients were identified - 70% were males and 93% were White; 139 (25%) received NAC (NAC+) while 434 (75%) did not (NAC-). NAC+ patients were younger (65 vs 71 years, p < 0.001). Downstaging to pT0-1N0 at the time of RC was significantly more frequent in the NAC+ group compared to the NAC- group (32 (24.5%) vs. 28 (6.8%), p = 0.001). Overall survival (OS) was also significantly longer in the NAC+ group (median of 40.8 vs. 19.4 months, log-rank p = 0.003). On multivariable analysis, NAC+ (Hazard Ratio (HR) = 0.73, 95% CI 0.56-0.91, p = 0.02), pathological downstaging to pT0-1N0 (HR = 0.5, 95% CI 0.31- 0.8, p < 0.001), and any pathological upstaging (HR 4.1, 95% CI 1.5-6.6, p < 0.001) were independently associated with all-cause mortality, while other factors were not (Table). Conclusions: In this large retrospective analysis, administration of NAC in muscle-invasive sarcomatoid bladder cancer was associated with higher rates of downstaging to non-muscle-invasive disease at the time of RC and reduced all-cause mortality. [Table: see text]

TPS406 Background: Most patients with high or very high risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). Neoadjuvant androgen ablation has not improved high-risk pathological features or recurrence rates after RP.1 We reported the association between high intratumoral CD8+ T lymphocyte (CTL) density and improved survival post-RP, suggesting clinical benefit from neoadjuvant immunomodulation (NI).2 Analysis of the tumor immune microenvironment after NI may also provide key insights into potential therapeutic strategies in PCa. CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9 and CXCL10) are downregulated while MDSC/Treg-attracting chemokines (CCL2, CCL22, and CXCL12) are upregulated in human PCa tissue.3 A large proportion of T cells in PCa are Tregs or dysfunctional CTLs and this immunosuppressive profile may be partly driven by COX-2 upregulation.4,5 A chemokine modulating regimen (CKM) of rintatolimod (TLR-3 ligand), aspirin (COX-2 inhibitor), and IFN-α favorably reprogrammed the chemokine profile and CTL/Treg ratio in human PCa explants.3 This combination has demonstrated safety in phase I/II trials across other tumor types, though it is unclear if IFN-α can be omitted without compromising efficacy.7-8 Methods: This is a three-arm, phase II trial where patients with localized PCa scheduled to undergo RP are randomized in 1:1:1 ratio to a 2-week regimen of neoadjuvant CKM triplet (rintatolimod + aspirin + IFN-α) vs CKM doublet (rintatolimod + aspirin) vs no CKM. Thirty patients will be enrolled to assess CD8+ T cell density in the RP specimen as the primary endpoint. Pathological and PSA responses, surgical margin positivity, and safety/toxicity of the CKM combinations will be secondary endpoints. Pre- and post-treatment density of various infiltrating T cell subtypes, MDSCs, chemokine and chemokine receptor profiles, immune checkpoint expression, immune-regulatory gene expression signatures, and peripheral blood immune cell landscape will be key exploratory endpoints. The trial is currently open with 11 patients enrolled. Clinical trial ID: NCT03899987 . References: 1) Scolieri MJ, J Urol 2000, 2) Clin Oncol 36, 2018: suppl; abstr 5068, 3) Muthuswamy R, Prostate 2016, 4) Sfanos KS, Prostate 2009, 5) Gupta S, Prostate 2000, 6) NCT01545141, 7) NCT02151448, 8) NCT02432378.

486 Background: UTUC is less common and associated with poorer stage-for-stage prognosis compared to urothelial bladder cancer. AC is regarded as a standard-of-care in high-risk UTUC based on superior disease-free survival compared to observation in the POUT trial, though fewer than 10% of patients in this trial had lymph node involvement.1 CheckMate 274 revealed lesser magnitude of benefit with adjuvant nivolumab in UTUC compared to bladder cancer on post hoc analysis.2 The preferred sequence of perioperative systemic therapy in node positive UTUC remains unclear. Methods: We queried the National Cancer Database for adult patients with clinically node positive (cTanyN1-3M0) UTUC diagnosed between 2004 and 2018. Patients were divided into two groups based on the perioperative treatment strategy - NAC or AC. Patients who did not undergo RNU were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 862 patients were identified - 362 (42%) underwent NAC while 500 (58%) received AC. No significant differences were noted between the groups regarding age, sex, or insurance status. Patients with cT1-2 UTUC more often received NAC (27.9% vs 11.8%, P

113 Background: The prognosis of refractory mCRPC remains poor despite advancements in therapeutic options. KeyNote-199 demonstrated modest activity of Pem in mCRPC with expected safety profile. We present our real-world experience with Pem in mCRPC. Methods: We conducted a retrospective review of mCRPC patients treated with Pem at our institution from 1/1/2017 to 10/1/22. Baseline demographic, clinicopathologic, and genomic characteristics were recorded. PSA and radiographic responses were assessed by the study team, and survival distributions estimated using the Kaplan-Meier method. Results: A total of 39 patients were identified – 97% (37) were White, median age was 71 years, 4% (19/35) had a Gleason Score ≥8; 80% (31) had skeletal and 74% (29) had soft tissue metastases at Pem initiation. Overall, patients were heavily pre-treated (median of 7 prior therapies, range 0-8) - 87% (34) had received taxanes, 82% (32) novel antiandrogens, 23% (9) Ra-223, 21% (8) Sipuleucel-T, and 2% (1) Olaparib. Median duration on Pem was 7 months (range = 1-29). Among the 34 evaluable patients, 2 (6%) achieved CR, 2 (6%) had PR, 5 (15%) had stable disease (SD), and 25 (73%) had progressive disease (PD) on radiographic assessment. PSA reduction ≥ 50% was noted in 7/32 (22%) patients. The 4 patients who had radiographic CR/PR had positive predictive biomarkers – Patient 1: CR – MSI-H, high TMB (17.5/Mb); Patient 2: CR – MSI-indeterminate, germline MSH6 mutation; Patient 3: PR – MSI-H, high TMB (28.8/Mb), germline MSH2 mutation; and Patient 4: PR – MSI-S, high TMB (18.3/Mb), PDL1 TPS 100%, positive neuroendocrine markers. Interestingly, patient 3 was switched to ipilimumab + nivolumab after PD on Pem, and subsequently had a CR. None of the evaluated patients with SD or PD had high MSI, TMB, or PDL1 levels. The median overall survival from Pem initiation was 4.4 months (95% CI 3.0-10.2 months). Three (8%) patients discontinued Pem due to immune-related adverse effects (IRAEs); no treatment-related deaths were reported. The most frequent Gr 3 IRAEs are shown. Conclusions: Single-agent Pem demonstrated modest overall efficacy in mCRPC, restricted only to patients with predictive biomarkers. Given the non-trivial risk of IRAEs, financial toxicity, and potential QoL implications, we suggest using checkpoint inhibitors only in appropriately biomarker-selected patients with mCRPC. [Table: see text]

487 Background: Upper urinary tract cancers (UUTC) are less frequent and associated with poorer stage-for-stage prognosis compared to bladder cancer, with variant histology being an independent predictor of inferior outcomes. The POUT trial included only patients with predominantly urothelial tumors. We aimed to compare outcomes among patients with UUTC-VH who were treated with RNU-AC vs. RNU-O. Methods: We queried the National Cancer Database for adult patients with UUTC-VH diagnosed between 2004 and 2018. Only patients who underwent RNU with node-negative disease on pathological staging (pT2-4N0M0) were included and divided into two groups based on the postoperative treatment strategy - RNU-AC and RNU-O. Patients who received neoadjuvant chemotherapy were excluded from analyses. Fisher’s exact and Mann Whiney U tests were used to compare frequency distributions. Cox Proportional Hazards regression was employed for multivariate analysis of factors associated with overall survival. Models were adjusted for age, sex, race, income, educational level, clinical T stage, insurance status, and the Charlson Comorbidity Index. Results: A total of 522 patients were identified – 133 (25.5%) received RNU-AC while 389 (74.5%) underwent RNU-O. Patients in the RNU-AC group were younger (median 69 vs. 76 years, P

343 Background: The population of prostate cancer (PCa) survivors has grown over the recent decades, with many reporting long-term treatment-related physical, emotional, and financial adverse effects resulting in greater psychological distress compared to males without a history of PCa. This study analyzes the prevalence of psychological distress among PCa survivors and its impact on emergency room (ER) utilization and overall survival. Methods: We identified a cohort of 3,453 PCa survivors from the 2000-2018 National Health Interview Survey (NHIS) linked to the National Death Index Mortality Files through Dec 31, 2019. Deaths that occurred during the first two years of follow-up were excluded from analyses to minimize the likelihood of reverse causation. The Kessler Psychological Distress Scale (K6) was used to quantify psychological distress. Severe, moderate, and none/low mental distress have been validated for thresholds K6≥13, 13> K6 ≥5, and 5> K6 ≥0. Its association with self-reported ER utilization during the 12 months preceding the survey and all-cause mortality was estimated using weighted multivariable logistic regression and Cox proportional hazards regression, respectively. Models were adjusted for age, sex, race, educational attainment, comorbidities, region, year of survey, smoking status, health insurance, functional limitations, and time since cancer diagnosis. Results: Among the 3,453 PCa survivors (mean [SD] age 68.5 [7.2] years; 2479 (77.9%] non-Hispanic White, 655 (14.1%) non-Hispanic Black; median time since cancer diagnosis:5 years), 435 (11.3%) and 96 (2.4%) reported moderate and severe psychological distress respectively. PCa survivors with psychological distress tend to be younger, less educated, single, and with multiple comorbid conditions, and functional limitations. 812(22.8%) of PCa survivors visited the ER during 12 months preceding the survey. During a median follow-up of 81 months, 937(25.5%) of survivors died of all causes. After adjusting for covariates, PCa survivors with severe psychological distress were at a higher risk of ER utilization and all-cause mortality than those with moderate or no distress. Conclusions: Psychological distress was associated with increased risk of ER utilization and all-cause mortality among PCa survivors. Greater efforts are needed to understand, recognize, and alleviate such distress, as well as to enhance social and mental/physical health support in this rapidly growing community of vulnerable cancer survivors. [Table: see text]

Background Patients who have attained pathological complete response (pCR) have a better prognosis when compared to those with residual disease (RD) after neoadjuvant chemotherapy. We analyzed the association between race and survival rates among different breast cancer subtypes for patients who attained pCR and those with RD. Methods We queried the National Cancer Database for early breast cancer (BC) patients who received neoadjuvant chemotherapy from 2010 - 2016. Demographic and clinical data were summarized by race for patients who attained pCR or those with RD. All associations were compared using Kruskal-Wallis, Pearson’s Chi-Squared, and Fisher’s Exact Tests. Multivariate cox models were generated for the overall survival, adjusting for age, sex, grade, stage, insurance status, facility type, treatments received including hormonal treatments, radiation, chemotherapy, and comorbidities. All analyses were conducted in RStudio v4.0.2 at a significance level of 0.05. Results A total of 137,881 patients were analyzed (females: 137,140, males: 741). 69.6% were White (n= 95,909), 17.2% Black (n=23,736), 8% were Hispanics (n=11,023), 4% were Asians (n=5,401) and 1.2% (n= 1812) others. Majority of the patients had stage II BC (56.4%, n= 79131), followed by stage III (30.7%, n= 42307) and stage I (12.9%, n= 16443). Blacks had lower odds (OR= 0.96, CI= 0.92-0.99, p= 0.02) while Asians had higher odds of attaining pCR (OR= 1.071, CI = 1.01 - 1.13) when compared to Whites. Among Whites who attained pCR, the 3-year (yr) and 5-yr survival rates (SR) in the HR+HER2-, HER2+, TNBC subtypes were encouraging at 95% & 90%, 97% & 94%, 94% & 91% respectively (rsp) (P < 0.001). Similarly, among Blacks who attained pCR, these SR were 94% & 90%, 96% & 92%, 94% & 91% rsp (P < 0.001). Among Asians who attained pCR, these SR were 99% & 98%, 98% & 96%, 96% & 92% rsp (P Citation Format: Arya Mariam Roy, Kristopher Attwood, Shipra Gandhi. Racial disparities in the attainment of pathological complete response in early breast cancer subtypes after neoadjuvant treatment and the differences in survival: A population-based study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C123.

Alpelisib is a phosphoinositol-3-kinase alpha catalytic subunit (PIK3CA) inhibitor used in patients with PIK3CA mutated breast cancer. The phosphatidylinositol 3-kinase (PI3K) pathway is responsible for activating protein kinase-B (AKT), and activated AKT promotes translation of glucose transporter 4 and glycogen synthesis in insulin-responsive tissues. Therefore, it is perhaps not surprising that hyperglycemia is the most common side effect of alpelisib, though diabetic ketoacidosis (DKA) appears to be a rare complication. This case describes the unique presentation of a patient with no prior history of diabetes who presented with DKA after starting alpelisib, and returned to euglycemia off of insulin just three days after stopping the drug suggesting that alpelisib can cause DKA in patients who did not previously have diabetes, and that the hyperglycemia is completely reversible upon discontinuation of the PIK3CA inhibitor and consequent restoration of the PI3K/AKT pathway.

165 Background: Pathological Complete Response (pCR) after Neoadjuvant Chemotherapy (NAC) is associated with improved survival outcomes in early-stage breast cancer. However, data regarding the factors predicting pCR are limited. We analyzed the clinical and pathological factors associated with the attainment of pCR after NAC. Methods: We queried National Cancer Database for non-metastatic breast cancer patients who received NAC between 2010 and 2016. All associations were compared using Kruskal-Wallis, Pearson’s Chi-Squared, and Fisher’s Exact Tests. Multivariate logistic models were used to analyze association of race, sub-type, age, clinical stage, grade, histology, insurance, comorbidity index with pCR. Odds ratios, 95% confidence intervals, and p-values for each predictor were recorded and adjusted for confounders. All analyses were conducted in RStudio v4.0.2 at a significance level of 0.05. Results: A total of 137140 female and 741 male patients were identified. Majority of the patients were Whites (n = 95909) followed by Blacks (n = 23736), and Hispanics (n = 11023). 58.4% (n = 80556) patients were > 55 years. 64% of the patients had private insurance, 31.1% (n = 42930) had government insurance (Medicare and Medicaid) and 3.6% (n = 4904) were uninsured. Majority of the patients had Charlson comorbidity index (CCI) equal to 0 (87%). Hormone-receptor positive and HER2 negative (HR+HER2-) comprised 37.9% (n = 51283), HER2+ were 35.2% (n = 47794) and triple-negative breast cancer (TNBC) were 26.9% (n = 36401). Compared to TNBC, HER2+ had higher and HR+HER2- had lower chance of attaining pCR. Blacks had lower (OR = 0.95, p < 0.001) and Hispanics had higher chance of pCR (OR = 1.1 p < 0.001) when compared to Whites in the overall population which includes all subtypes. Younger patients had lower chance of attaining pCR compared to elderly. Stage I and II patients had more chance of PCR compared to stage III. Patients with government insurance had lower odds of attaining PCR compared to those with private insurance. Patients with CCI 0 had higher chance of pCR when compared to those with CCI > = 3 (OR = 1.15, 95% CI = 1.08-1.2, p < 0.001). Conclusions: Patient and tumor factors play an important role in response to NAC in breast cancer patients. Identifying modifiable factors associated with odds of lower pCR rates such as, government insurance would help us intervene to improve the quality of care of breast cancer patients.[Table: see text]

The new drug approval in every country is closely monitored and regulated by central authorities which regulates drug development, approval, and marketing. In this study, we aim to analyze and compare the approval status of drugs that are approved for medical use in India by the Central Drugs Standard Control Organization (CDSCO) with the drug approval organizations of Western Countries.We conducted a retrospective cross-sectional study. We queried the CDSCO website and database for new drugs and anti-cancer drugs that are approved for use in India by CDSCO during 2010-2019. We compared the approval status of those drugs in the FDA (Food and Drug Administration), EMA (European Medicines Agency), and Health Canada (HC) databases.A total of 257 new drugs (including 47 anti-cancer drugs) are approved for use in India by the CDSCO during the period 2010-2019. Out of these, only 69.6% (n = 179) new drugs were approved by the FDA, 62.65% (n = 161) were approved by EMA and 63.40% were approved by Health Canada (n = 163). Most of the anti-cancer drugs that are approved for use in India are approved by these agencies except 2 drugs that are not approved by FDA and HC.Majority of cancer drugs approved for use in India are approved for use in the USA, Europe and Canada. However, a significant number of non-cancer drugs approved for use in India are not approved in these regions.We recommend a comprehensive assessment of India's drug regulatory processes and policies to improve patient safety.

Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next-generation flow cytometry (sensitivity of 10−5 cells) at 3- to 6-month intervals. With a median follow-up of 9.9 years from diagnosis (range, 0.4-30.9), 61% of patients maintained MRD negativity, whereas 39% experienced MRD conversion at a median of 6.3 years (range, 1.4-25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95% vs 84%; P = .001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 years (range, 0-4.9). However, 27% of MRD conversion-positive patients had not yet experienced a clinical relapse, with a median follow-up of 9.3 years (range, 2.2-21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared with patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

Intravascular large B-cell lymphoma is a rare malignancy characterized by the presence of lymphoma cells within the lumen of blood vessels. The annual incidence of cases is fewer than 0.5 cases per 1,000,000. It usually affects the elderly with an average age of diagnosis around 70 years. Due to the absence of lymphoma cells in the peripheral smear and lymphadenopathy, it is difficult to diagnose these cases. Although the central nervous system and skin are the commonly involved organs, they can involve any organ system. Prompt diagnosis and initiation of treatment are very crucial as it carries a high mortality. We describe two patients who presented with constitutional symptoms and fever of unknown origin, later diagnosed as intravascular large B- cell lymphoma. The diagnosis was difficult in both cases as the presenting symptoms were atypical. One of the patients was diagnosed at autopsy. The delay in diagnosis often leads to fatal outcomes as the disease is very aggressive. A high degree of clinical suspicion is the key to prompt diagnosis and improved outcomes.

606 Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a surrogate predictor for long-term survival in breast cancer (BC). Patients who attain pCR have improved relapse-free and overall survival (OS) when compared to patients with residual disease (RD). We examined the pCR in Black and White BC patients who received NACT and their OS after attaining pCR and RD. Methods: The National Cancer Database (NCDB) was queried for Black and White females with non-metastatic BC from the years 2010 – 2016 who received NACT. Logistic regression was used to analyze pCR/RD and Cox proportional hazards regression to analyze OS, with adjustment for age, race, stage, grade, body mass index, treatments received, insurance status and comorbidities. STATA/IC 16.0 was used for analysis and a two-sided p-value < 0.05 was considered significant. Results: A total of 101,014 White and Black BC patients were identified, including 24,852 (Whites - 74.43%, Black - 25.57%) triple negative breast cancer (TNBC), 51,043 (Whites - 84%, Blacks - 16%) hormone receptor positive HER2 negative (HR+HER2-) and 17,818 (Whites - 83%, Blacks - 17%) HER2 positive. Whites had a slightly higher odds of attaining pCR compared to Blacks (adjusted Odds Ratio (aOR) = 1.040, 95% Confidence Interval (CI) = 1.02 - 1.19, p = 0.02). The difference was largest in TNBC subtype (TNBC: aOR = 1.34, 95% CI = 1.20 - 1.56, p < 0.001; HR+HER2-: aOR = 1.1; 95% CI = 1.02 - 1.32, p = 0.038; HER2+: aOR = 1.13, 95% CI = 1.08 - 1.27, p < 0.001). Among those who attained pCR, Blacks had worse OS when compared to Whites in HER2+ subtype (adjusted Hazard Ratio (aHR) = 1.41, 95% CI = 1.04 - 1.93, p = 0.028) but not in TNBC or HR+HER2- subtypes. Among those with RD, Blacks had worse OS in the whole cohort compared to Whites (aHR = 1.43, 95% CI = 1.26 - 1.58, p < 0.001), and in all subtypes: TNBC (aHR = 1.17, 95% CI = 1.11 - 1.23, p < 0.001), HR+HER2- (aHR = 1.38, 95% CI = 1.31 - 1.45, p < 0.001) and HER2+ (aHR = 1.45, 95% CI = 1.32 - 1.59, p < 0.001). Conclusions: Black BC patients with TNBC were less likely to achieve pCR than Whites after NACT. When Black patients with HER2+ subtype did attain pCR, they still had worse OS than Whites. The same racial difference in OS was observed in all BC subtypes - TNBC, HR+HER2- and HER2+ among patients with RD. This highlights the importance to investigate novel personalized treatment strategies for Black patients.

4586 Background: Non urothelial cancers and urothelial cancers with variant histologies(NUVH) have a more aggressive natural history and are at a higher risk of progression to muscle invasive disease(MIBC) when compared to their urothelial counterparts. Although surgical resection is the treatment of choice in localized disease, radiation(RT) is commonly used in patients who are not surgical candidates. The use of chemotherapy has shown modest benefit in some retrospective studies. Considering the low incidence of NUVH, there are no large-scale studies examining the benefits of chemoradiation(CRT) in MIBC with NUVH. Methods: The National Cancer Database was queried to identify MIBC patients with NUVH from the years 2004-2018.Inclusion criteria for the study are age > 18 years, Non urothelial or variant histologies and receipt of RT. Patients who underwent cystectomy or had metastatic disease were excluded. The population was divided into two cohorts if they received chemoradiation. Chi-Square test and Mann Whitney U tests were used to compare frequency distributions. Cox proportional Hazard regression was employed to control for confounding factors associated with overall survival. Covariates for confounding included age, race, sex, income, insurance status, charlson-deyo comorbidity index, education. Results: Among 1773 observations in the final analysis, 63.05%(n = 1118) received CRT. Small cell, large cell and neuroendocrine cancers composed of the majority of NUVH. 38.01% (n = 641). Other histologies composed of squamous cell cancer 30.34%(n = 538), spindle cell/sarcomatoid cancers10.15%(180), adenocarcinoma 11.44%(203). Patients who received CRT were found to be significantly younger (76 vs 82 years P: < 0.0001) with higher male predominance74.73%. 5 year overall mortality was significaantly lower in the CRT vs RT group ( 66.47% vs 81.55%, p < 0.001). After controlling for confounding factors, CRT was associated with lower risk of mortality Hazard Ratio(HR)of 0.41(0.36-0.47) p < 0.0001. Added, the survival benefit of CRT continued in the non small cell variant cohort HR: 0.43(0.37-0.51) P < 0.0001. Conclusions: In this large retrospective study, CRT was associated with reduced overall mortality among patients with non-urothelial MIBC. The findings suggest the importance of systemic therapy in providing a survival advantage to non-urothelial MIBC, including the non-small cell variants. [Table: see text]

e18614 Background: With longer median survival for NET patients, the impact of symptoms and treatments on QOL and financial well-being throughout the disease course need to be evaluated to understand the true burden of the disease on patients. Current HRQOL data are during active treatments and this prospective biobank was established to capture this information throughout the disease course. Methods: At Roswell Park Comprehensive Cancer Center, with Institutional Review Board (IRB) approval a NET biobank was established in April 2019 for collecting clinical tissue samples, patient demographics, treatment outcomes, access to care and self-reported HRQoL outcomes. Using previously developed HRQoL questionnaires, we examined the impact of the NET on the quality of life of NET patients and data of 144 patients enrolled to date in the biobank is presented here. Linear regression was used to assess the association of baseline characters with QoL variables. The analysis was done with STATA/IC 16.0. Results: A total of 144 patients are enrolled. Males were 27% (n = 39) and females were 73% (n = 105). The mean age of diagnosis was 54 +/- 0.79, with those between 45 to 65 (72%, n = 103). These patients were enrolled through support groups and social media from 30 different states in the US (135) and 9 pts from Canada. After the diagnosis, 27% of patients had to quit their job. Impact on major HRQoL variables are summarized in Table. Only 21% of patients reported that they feel knowledgeable about NET and got the majority of their support from their primary care (60%) and oncologist (57%). When asked about the most pressing need from their care team, 57% of patients requested their care team had more information about available clinical trials. Sex, age groups did not have statistically significant association on the impact of NETs on the HRQoL of patients. Conclusions: NET diagnosis affects the HRQoL of patients including their social, emotional, and financial well-being. A national biobank capturing data on various demographic, risk factors, treatment sequence, symptoms, HRQoL parameters, financial toxicity is a valuable resource to better understand the needs of this patient group.[Table: see text]

Introduction Acquired amegakaryocytic thrombocytopenia (AATP) is a rare bleeding disorder that causes severe thrombocytopenia with preserved hematopoiesis of other cell lineages. Many cases are misdiagnosed and treated as immune thrombocytopenia. Case presentation We report a case of AATP, in a 50-year-old man, that was treated as immune thrombocytopenia for years with no clinical response. The disorder later was diagnosed as AATP after bone marrow biopsy and was successfully treated with cyclosporine. Discussion The exact mechanism of AATP remains unclear; it is suspected to be an immune-mediated process. Patients with AATP present with severe bleeding and thrombocytopenia, which is usually unresponsive to high-dose corticosteroids. There are no standard treatment guidelines for AATP. Cyclosporine and antithymocyte globulin are found to be effective in some cases. The prompt diagnosis of AATP is vital because it carries high mortality because of excessive bleeding, and it can progress into aplastic anemia or myelodysplastic syndrome.

Case Presentation A 44-year-old woman was referred for evaluation of dyspnea on exertion and multiple nodular opacities on a chest CT scan. She had a medical history of autoimmune encephalitis, diabetes mellitus, hypertension, migraines, and allergic rhinitis. Ten years earlier, the patient was admitted to an outside institution with symptoms of shortness of breath. She was found to have multiple pulmonary nodules and was diagnosed empirically with and treated for sarcoidosis. She was told that her pulmonary nodules had improved on follow up. However, she continued to have symptoms of dyspnea. Due to progressive symptoms of shortness of breath, she was referred to pulmonology. She reported a weight gain of 80 pounds over the last year. She denied fever, chills, hemoptysis, night sweats, joint swelling, or skin rash. She is a former cigarette smoker with a 15 pack-year smoking history, quit smoking in 2005. She denied alcohol or drug use. She resided in Arkansas and Texas over the past decade. She previously worked as a teacher and is currently unemployed. She had no other relevant exposures. She denied a family history of autoimmune diseases or malignancies.

Background Atypical HUS (aHUS) is a rare thrombotic microangiopathy (TMA) caused by complement dysregulation. Eculizumab is a humanized monoclonal antibody targeting against complement factor C5. Ravulizumab, a longer acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for treatment of aHUS in 2019. Here we describe the clinical presentation, laboratory, genetic profile, treatment along with long-term sequelae of patients diagnosed with aHUS. The outcomes of restrictive use of eculizumab and the use of ravulizumab were also studied. Materials and Methods We conducted a single center retrospective cohort study, searching electronic medical records of patients diagnosed and treated for aHUS at University of Arkansas for Medical Sciences, from January 1, 2013 to January 31, 2021, after IRB approval. Inclusion criteria :1) Presence of microangiopathic hemolytic anemia (MAHA) with thrombocytopenia 2) ADAMTS13 activity > 10 % 3) Age > 18. Exclusion criteria: 1) Age < 18 years 2) TMA associated with hemolytic uremic syndrome, scleroderma renal crises, anti-phospholipid syndrome. Results Seventeen patients meeting the inclusion criteria were enrolled in the study. The mean age at diagnosis was 47.4 ± 17.9 years. Most of the patients were Caucasians (n=10, 58%) and females (n= 14, 82%). All the patients except one had acute kidney injury (AKI) at presentation (n=16, 94.1%), the most frequent extra-renal presentation was CNS involvement -seizures, confusion and altered mental status (n= 7, 41.2 %) followed by Gastrointestinal- non-bloody diarrhea, nausea and vomiting (n=5, 29.4 %) [Figure 1]. Lab investigations are described in [Table 1]. Complement genetic testing was done in 100% of study population. Factor H related genes 1/3 (CFHR1/3) and complement factor H (CFH) were the most commonly found pathogenic mutations [Table 2]. In this study, pregnancy and infection (n= 4, 23.5% each) were identified as the most common triggers [Figure 2]. For two of the patients, it was the first pregnancy and for the other two, it was their second and third pregnancies. They presented at the second, sixth, and sixteenth week postpartum respectively. Eleven (64.70%) patients developed chronic kidney disease (CKD) with six (35.29%) patients progressing to end stage renal disease (ESRD). Two (11.76 %) pregnant patients developed cardiomyopathy, two (11.76%) patients developed pulmonary complications (pneumonia and pulmonary hypertension) and three (17.64%) patients developed epilepsy. All the postpartum females in our study were able to breastfeed while on eculizumab with no long-term complications in the neonates. One patient had two subsequent deliveries with no ante, intra, or post-partum consequences or repeated triggers of aHUS. Fourteen patients (82.3%) received therapeutic plasma exchange, four (23.5%) patients received iv methyl prednisone (1mg/kg) and two (11.7%) patients received IVIg prior to initiating eculizumab. Over time, five (29.41%) patients opted to completely stop drug therapy and four patients (23.52%) chose to shift to ravulizumab because of the ease of treatment duration (every 8 weeks rather than every 2 weeks for eculizumab). All these nine patients remained in remission with stable hematologic and renal parameters on subsequent follow-ups [Table 3]. Three patients (17.6 % mortality) died in our study due to causes unrelated to aHUS. Conclusions: The clinical diagnosis of atypical HUS can be challenging especially with extra-renal manifestations. Females were four times more affected than males. PCMs were present in 11 patients. Early diagnosis and treatment with C5 inhibitors improves morbidity and mortality. The decision to discontinue or switch eculizumab to ravulizumab will likely decrease healthcare costs and improve patient compliance but should be based on disease severity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

BACKGROUND Heavy chain diseases (HCDs) are B-cell neoplasms characterised by production of monoclonal (M) protein consisting only of immunoglobulin heavy chain without a bound light chain. Three types have been recognized- IgA alpha HCD (most common, a form of extra nodal marginal zone lymphoma of mucosal associated lymphoid tissue aka immunoproliferative small intestinal disease [IPSID], Mediterranean lymphoma or Seligmann disease], IgG gamma HCD (aka Franklin's disease, variant of lymphoplasmacytic lymphoma) and IgM mu HCD (rarest, resembles chronic lymphocytic leukemia). Limited data is available regarding the epidemiology, survival patterns, and incidence of second primary malignancies in patients with HCD in the Unites States. MATERIALS AND METHODS We performed a retrospective analysis using SEER* stat version 8.3.9 statistical software and November 2020 submission of SEER 18 registry which covers ~ 27.8 % of US population based on the 2010 census. We identified all cases > 1 years old diagnosed with Heavy chain disease between 2000 and 2018 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9762/3. We analyzed survival using Kaplan- Meier method, and MP-SIR session was used to calculate the risk of second primary malignancy. RESULTS A total of 64 cases of HCD were identified. Most common primary sites of involvement were bone marrow (82.8%), lymph nodes (9.3%), GI tract (3.1%), others (4.6%)- spleen, blood and vertebral column. The crude, age-adjusted to 2000 US standard population and age-specific incidence rate of HCD in the United States is < 1/100,000 respectively. The median age at diagnosis is 68 years with incidence in males being about 1.3 times that of females. Bimodal age distribution was observed, with peak incidence between ages 60-64 and 75-79 [Figure 1]. In our entire cohort, 82.8% (n=53) patients were Caucasians, 15.6 % (n=10) patients were African Americans, and 1.5% (n=1) patients were American Indian/Alaska Native. Among Caucasians, 56.6% (n=30) patients were males, and 43.3% (n=23) patients were females. Between 2000-2018, the maximum cases (n=7 each) were diagnosed in the year 2002 and 2008 [Figure 2] The median overall survival for the entire cohort was 48 months (95% CI: 35- 61). Overall survival rates of all ages, sex and race at 1 year, 2 year and 5 years were found to be 86.1%, 71.4%, 57.8% respectively. OS at 5 years declines after 70 years .Patients with HCD are at risk of developing subsequent solid and haematological malignancies within 5 years of diagnosis. 9 (14 %) cases developed SPMs: urinary bladder (n=1), lung and bronchus (n=2), Hodgkin-nodal (n=1), Non-Hodgkin Lymphoma -extra nodal (n=1), GI cancers [stomach (n=1), esophagus (n=1) and ascending colon (n=1)], miscellaneous (n=1). [Figure 4]. The mean follow-up duration for new SPM was 51 months. Overall, 39 patients died: 3 (4%) from miscellaneous malignant cancer and 11 (17%) patients from haematological malignancy; the most common being Non-Hodgkin lymphoma (n=8), followed by Hodgkin lymphoma (n=1), Multiple myeloma (n=1) and leukemia (n=1). CONCLUSIONS HCD is an extremely rare haematological malignancy. The incidence of HCD is proportionately higher among Caucasians as compared to other races, with no reported case among Asian or Pacific Islanders. Among Caucasians, males and females have approximately equal risk of acquiring HCD. Most patient die because of their primary haematological malignancy. We recommend close follow-up for at least the first 5 years after initial diagnosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction Peripheral T-cell lymphoma (PTCL) is diverse group of an uncommon and aggressive type of non-Hodgkin lymphoma (NHL). It generally affects people aged 60 years and above and is diagnosed slightly more often in men than in women. However, younger adults and children are also diagnosed with PTCL. Being a rare entity, the best treatment regimen has not been established for newly diagnosed patients or for relapsed/refractory patients with PTCL. In general, treatment outcomes have been poor with conventional chemotherapy regimens. Methods We performed a retrospective cohort study of patients with newly diagnosed and relapsed PTCL, and its subtypes, who are seen in the hematology-oncology clinic at the University of Arkansas for Medical Sciences from July 2014 to December 2019. The demographics of the study population, the frontline and second-line treatment strategies for all the subtypes and the response to the treatment were studied. Also, the role of high dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) in the overall survival (OS) and progression-free survival (PFS) is analyzed. Results Out of the 48 patients, 45.8% (n=22) patients had PTCL not otherwise specified (PTCL NOS) type, 29% (n=14) had Anaplastic large cell lymphoma ALK-negative subtype, 4.2 % (n=2) had Anaplastic large cell lymphoma ALK-positive subtype, Angioimmunoblastic T-cell lymphoma, Extra nodal NK/T cell lymphoma, Enteropathy associated T- cell lymphoma each. The mean age of diagnosis was 58 ± 2. Males were affected more when compared to females (66.6% vs 33.3%). Also, Caucasians were more affected than African Americans (73% vs 25%). The mortality of PTCL was found to be 40%. After frontline treatment, complete response (CR) was observed in 43.7% (n= 21) patients, partial response (PR) was observed in 18.7% (n= 9) patients, stable disease (SD) was seen in 4% (n=2), progression of disease (PD) was observed in 12.5% (n= 6) patients. Stem cell transplant (HDT-ASCT) was done for 28% (n=13) of patients who achieved CR after frontline chemotherapy (CR1). Relapse was observed in 60% of patients. Patients with stage III and IV on the initial diagnosis had a higher chance of relapse or refractory disease. After the second-line treatment, out of 20 patients, 9 patients had CR, 5 had PR, 5 patients had PD, 1 patient had SD. CR was observed in 7 patients with either brentuximab vedotin alone or brentuximab vedotin with combination chemotherapy as second-line treatment. The OS and PFS were found to be higher in patients who received HDT-ASCT after CR1. Conclusion PTCL has a high risk of relapse and there are no uniform guidelines for the treatment of PTCL in relapsed or refractory setting. The currently available second line treatment options have shown modest response rates. Our study has shown that brentuximab vedotin, when used alone or in combination, showed better response rate in the relapsed setting. Also, stem cell transplant improved the overall survival and progression-free survival in patients with PTCL after frontline chemotherapy. Disclosures No relevant conflicts of interest to declare.

Acquired inhibitors of coagulation are a group of rare but potentially life-threatening blood disorders characterized by the presence of autoantibodies directed against clotting factor. Autoantibody against factor VIII is the most common form of clotting factor inhibitor, a condition also known as acquired hemophilia A. We present a clinical series of nine patients diagnosed and treated for acquired hemophilia A at our institution. Among these nine patients, there were five men and four women with a median age of 64 years. All patients presented with bleeding diathesis. Factor eight inhibitor bypassing agent and/or recombinant factor VIIa were predominantly used for control of active bleeding. For elimination of autoantibodies, either steroids alone or the combination of steroids with rituximab or oral cyclophosphamide was used. Despite aggressive measures, two of the patients had a poor outcome; seven of the nine patients (77%) had a good clinical outcome. Acquired hemophilia A should be strongly suspected in any patient presenting with bleeding and a prolonged activated partial thromboplastin time. Early initiation of factor bypassing agents such as activated prothrombin complex concentrates or recombinant factor VIIa, along with the use of immunosuppressive agents, can be lifesaving.

Background Non-publication of clinical trials gives rise to publication bias which distorts data available in medical literature. Prior research indicates that a large number of clinical trials remain unpublished. We conducted a study to determine the publication rate of clinical trials related to cancer which were registered in the Clinical Trials Registry-India (CTRI), the clinical trials registry of India. Methods We performed a cross-sectional analysis of CTRI to determine publication rates. We searched CTRI for completed interventional clinical trials related to cancer. A comprehensive search for publications of the registered trials was performed by three different investigators. We considered a trial to be published if the study or any outcome data pertaining to the study was accepted for publication in a peer-reviewed journal. Results 73 of the 133 trials (54.9 %) included in our study were published. Randomized controlled trials were more likely to be published than non-randomized trials (61 % vs 34 %, p 0.007). Trials funded by international pharmaceutical companies were more likely to be published than the ones by Indian pharmaceutical companies (72 % vs 24 %, p Conclusion Large number of cancer clinical trials remain unpublished. This could be due to reluctance on the part of the investigator to publish statistically non-significant results, and sometimes to protect intellectual property. There is much scope for improvement in the rates of trial publication and information dissemination.

8514 Background: Attainment of MRD negativity in multiple myeloma (MM) patients is increasingly considered an optimal therapeutic endpoint, but little is known about the MRD evolution in those who achieve this milestone. We investigated the clinical implication of loss of MRD negativity or MRD conversion in patients with ≥VGPR. Methods: We identified and followed 606 patients achieving a sustained ≥VGPR with bone marrow MRD negativity(≥ 2 consecutive reading) following treatment on a total therapy protocol and with a median follow-up of 10 y. All patient had negative PET and MRI DWIBS at enrollment. Serial BM aspirate MRD was determined by 8-color next generation flow (NGF, EuroFlow) with a minimal sensitivity of 10−5 cells. Results: Most MM patients were considered low risk with a UAMS GEP70 score of ≤ 0.66 (92%; 495/538) . While 60% (364/606) of patients had sustained MRD negativity, the remaining 40% (242/606) experienced MRD conversion with a 5.7 y median time from ASCT and 6.3 y from diagnosis. The risk of clinical relapse was significantly elevated in patients with MRD conversion compared to sustained MRD negativity (73%, 177/242 vs. 5%, 18/364; R.R. = 3.5; P< 0.0001). The median level of MRD positivity (> 0.2 ratio of MM cells to normal plasma cells) also highly correlated with relapse ( P< 0.0001). Loss of MRD negativity preceded clinical relapse by a median time of 1.1 years. Loss of MRD negativity without clinical relapse was seen in 27% (65/242). MRD conversion was associated with an inferior PFS and OS (PFS: 10.2 y vs. NR; P < 0.0001, H.R. 18.7; 95% CI 13.3 - 26.3 and OS: 26.1 y vs. NR; P= 0.01, H.R. 1.7; 95% CI 1.1 - 2.6). Furthermore, when MRD conversion was within 5 y of diagnosis compared > 5 y, patients had a worse OS ( P < 0.0001, H.R. 17.2; 95% CI 7.8 – 37.8). We also observed that MRD conversion later than 5 years from diagnosis did not affect the OS. In a subset of patients (n = 144) the timing of first MRD negativity following treatment was available. Attainment of MRD negativity within 6 months of diagnosis compared to any time after 6 months was predictive of future MRD conversion (65%, 17/26 vs.42%, 49/118; P = 0.03) and clinical relapse (54%, 14/26 vs.28%, 33/118; P = 0.02). Conclusions: MRD conversion occurs in a significant proportion of MM patients (40%) on long-term follow-up and predicts future clinical relapse. Significance of MRD conversion has a temporal relationship from diagnosis and portray inferior clinical outcome particularly within 5 years of diagnosis.