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To examine patient and disease characteristics, toxicity, and clinical outcomes for patients with advanced urothelial carcinoma (aUC) who are rechallenged with immune checkpoint inhibitor (ICI)-based therapy.In this retrospective cohort, we included patients treated with ICI for aUC after having prior ICI treatment. Endpoints included the evaluation of radiographic response and disease control rates with first and second ICI courses, outcomes based on whether there was a change in ICI class (anti-PD-1 vs. anti-PD-L1), and assessment of the reasons for ICI discontinuation.We identified 25 patients with aUC from 9 institutions who received 2 separate ICI courses. ORR with first ICI and second ICI were 39% and 13%, respectively. Most patients discontinued first ICI due to progression (n = 19) or treatment-related toxicity (n = 4). Thirteen patients received non-ICI treatment between the first and second ICI, and 12 patients changed ICI class (anti-PD-1 vs. anti-PD-L1) at rechallenge. Among 10 patients who changed ICI class, 8 (80%) had progressive disease as best response with second ICI, while among 12 patients re-treated with the same ICI class, only 3 (25%) had progressive disease as best response at the time of rechallenge. With second ICI, most patients discontinued treatment due to progression (n = 18) or patient preference (n = 2).A proportion of patients with aUC rechallenged with ICI-based regimens may achieve disease control, supporting clinical trials in that setting, especially with ICI-based combinations. Future studies are needed to validate our results and should also focus on identifying biomarkers predictive of benefit with ICI rechallenge.

Immune checkpoint inhibitors are a well-established treatment option for advanced urothelial carcinoma, and biomarkers of response are needed for better patient selection. We show that metastatic disease confined to lymph nodes is associated with better outcomes, while metastases to liver, bone or both are associated with poor outcomes with immune checkpoint inhibitor therapy. Results are hypothesis-generating but relevant to practice. BACKGROUND: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. METHODS: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd(+) line. RESULTS: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd(+) line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd(+) line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. CONCLUSION: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

PDF file - 40K, Supplemental Table 1. Selected Demographic and Baseline Characteristics of the Patients. Supplemental Table 2. Selected Demographic and Baseline Characteristics of the HPV16 positive.

Purpose:Glutaminase is a key enzyme, which supports elevated dependency of tumors on glutamine-dependent biosynthesis of metabolic intermediates. Dual targeting of glucose and glutamine metabolism by the mTOR inhibitor everolimus plus the oral glutaminase inhibitor telaglenastat showed preclinical synergistic anticancer effects, which translated to encouraging safety and efficacy findings in a phase I trial of 2L+ renal cell carcinoma (RCC). This study evaluated telaglenastat plus everolimus (TelaE) versus placebo plus everolimus (PboE) in patients with advanced/metastatic RCC (mRCC) in the 3L+ setting (NCT03163667).Patients and Methods:Eligible patients with mRCC, previously treated with at least two prior lines of therapy [including ≥1 VEGFR-targeted tyrosine kinase inhibitor (TKI)] were randomized 2:1 to receive E, plus Tela or Pbo, until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed progression-free survival (PFS; one-sided α Results:Sixty-nine patients were randomized (46 TelaE, 23 PboE). Patients had a median three prior lines of therapy, including TKIs (100%) and checkpoint inhibitors (88%). At median follow-up of 7.5 months, median PFS was 3.8 months for TelaE versus 1.9 months for PboE [HR, 0.64; 95% confidence interval (CI), 0.34–1.20; one-sided P = 0.079]. One TelaE patient had a partial response and 26 had stable disease (SD). Eleven patients on PboE had SD. Treatment-emergent adverse events included fatigue, anemia, cough, dyspnea, elevated serum creatinine, and diarrhea; grade 3 to 4 events occurred in 74% TelaE patients versus 61% PboE.Conclusions:TelaE was well tolerated and improved PFS versus PboE in patients with mRCC previously treated with TKIs and checkpoint inhibitors.

Supplementary Figure from Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial

Supplementary Table from Telaglenastat plus Everolimus in Advanced Renal Cell Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled, Phase II ENTRATA Trial

Immune checkpoint inhibitors improve overall survival in advanced urothelial carcinoma, but response rates remain modest. We performed a multi-institutional retrospective cohort study comparing outcomes (observed response rate, progression-free, and overall survival) between patients based on time from initiation of first line platinum-based chemotherapy to second line immune checkpoint inhibitor. This study provides preliminary data that earlier resistance to platinum-based chemotherapy may be associated with shorter survival in those who receive subsequent ICI. BACKGROUND: Early progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC. PATIENTS AND METHODS: We performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3–6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3–6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02–2.63) and OS (HR 1.77; 95% CI 1.10–2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months. CONCLUSION: Among patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.

Background: Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes. Patients and methods: We performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression ; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors. Results: A total of 1026 patients with aUC were identified ; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings. Conclusion: Prior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.

34 Background: The American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) published a joint statement addressing clinical eligibility for characteristics lacking adequate representation in recent studies (Kim et al., Clin Cancer Res 2021). Herein, we aimed to identify the frequency of other potentially excessive exclusion criteria in the context of metastatic prostate cancer. Methods: The eligibility criteria of advanced prostate cancer studies with start dates between June 30, 2012 and June 30, 2022 were identified through Clinicaltrials.gov. MeSH (Medical Subject Headings) terms in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (prostate cancer OR prostate adenocarcinoma)”. Our study included trials conducted worldwide and examined patients aged 18 and over in phase I-III trials. To narrow the scope of study, trials including more than one cancer type (basket trials) as well as those focusing on radiation therapy were not included in the study. Descriptive statistics were used to determine the frequency of eligibility criteria while the Fisher’s exact test or chi-square test were performed to demonstrate association between type of treatment and exclusion criteria. Results: 265 of 699 (37.9%) clinical trials within the specified search had sufficiently available data for evaluation. Of these, 136 (51.3%), 51 (19.2%), 26 (9.8%), 20 (7.5%), 19 (7.2%), and 7 (2.6%) of trials investigated treatment with combination therapy, hormone therapy, targeted therapy, immunotherapy, radioligand therapy, and chemotherapy, respectively. The most common ASCO-FCR-cited exclusion criteria in the studies were brain metastases (161/265, 60.8 %), HIV positivity (123/265, 46.4%), HBV/HCV positivity (122/265, 46.0%), and concurrent malignancies (41/265, 16.6%). Statistically significant relationships were identified between type of treatment along with status of brain metastases, HIV, and HBV/HCV (p=0.011

612 Background: A consensus statement from the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (FCR) collaboration highlights the importance of expanding eligibility criteria in cancer trials to more accurately reflect the real-world population (Kim et al., Clin Cancer Res 2021). We sought to characterize use of overly restrictive eligibility criteria in renal cell carcinoma (RCC) trials in the context of ASCO-FCR recommendations. Methods: Studies containing the MeSH terms “(metastatic OR advanced OR stage IV or unresectable) AND (kidney cancer OR renal cell carcinoma OR renal cell cancer)” from June 30, 2012 to June 30, 2022 were identified on the ClinicalTrials.gov platform. Our search query’s inclusion criteria identified international studies examining adult patients aged ≥ 18 in phase I-III trials. Exclusion criteria comprised pan-cancer studies, trials involving localized treatments, radiation therapy, and prognostic tools. Descriptive statistics were used to characterize the frequency of restrictive eligibility criteria across studies, while Fisher’s exact test or chi-square test were utilized to determine the association between treatment type and exclusion criteria. Results: The content of 423 RCC trials were analyzed, of which 112 (26.5%) had adequate data available. 48 (42.9%), 44 (39.3%) and 18 (16.1%) studies examined combination therapy, targeted therapy, and immunotherapy, respectively. The presence of HIV positivity, HBV/HCV positivity, brain metastases, and concurrent malignancies accounted for the most frequently cited exclusionary criteria, seen in 83/112 (74.1%), 60/112 (53.6%), 37/112 (33.0%), and 9/112 (8.0%) studies respectively. Differences in the use of HIV positivity (p

662 Background: Mounting data suggests that dietary modification and supplement use, including probiotics, may modulate outcomes with immunotherapy in cancer therapy (Spencer CN et al. Science 2021; Dizman N et al. Nature Medicine 2022). For the first time, we sought to quantify the use of these measures among patients with metastatic renal cell carcinoma (mRCC). Methods: An online survey was administered by Kidney Cancer Research Alliance (KCCure), a non-profit patient advocacy group, between July 22 and Sept 22 to a patient mailing list (N=1,532). Only patients diagnosed with mRCC and under active systemic therapy were included for analysis in the current study. Select questions were directed at dietary modification patterns and supplement usage. Patients were additionally surveyed regarding out-of-pocket spending patterns related to supplement purchases and to what extent they shared information about their supplement intake with their physicians. The student's t-test and Chi-square test were used to compare sociodemographic characteristics between participants who did and did not report supplement intake. Results: Out of 1,062 patients with renal cell carcinoma who participated in this survey, 289 met the inclusion criteria (M:F, 145:143). The median age was 61. The majority of patients identified themselves as white (91%), were from the US (86.8%), and had completed a bachelor's degree (52.9%). 21.1%, 46.1%, and 32.6% lived in urban, suburban, and rural locations, respectively. The most common reported first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). 22.4% of respondents reported spending >$100/month on supplements, and 8.3% reported spending >$250/mo. Dietary modifications following a cancer diagnosis were reported by 34.9% of respondents, out of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. 50.8% of respondents reported supplement intake. The most widely utilized supplements were cannabidiol (CBD) oil/marijuana, probiotics, and Vitamin C, reported by 28.0%, 24.2%, and 18.6% of respondents, respectively. 83.4% of respondents noted that they consistently report supplement usage to their physicians. There were no statistically significant associations between supplement use and age, sex, living area, or education. Conclusions: A substantial proportion of patients with mRCC use dietary modification and supplements as an adjunct to their antineoplastic treatment. Interventions such as probiotic use and ketogenic diets, which are the subject of a prospective study in mRCC (NCT05119010; NCT05122546), may already be used by many patients. More careful attention to nutrition and supplement use in clinical trial candidates may minimize the impact of these potential confounders.

453 Background: American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) underscored the need to broaden eligibility criteria in cancer trials to increase patient accrual, expand access to investigational treatments, and enhance generalizability of study results (Kim et al., Clin Cancer Res 2021). While eligibility criteria intend to prioritize patient safety and define a specific study population, these criteria are often based on outdated standards and may not be reflective of real-world practice. Our study aimed to characterize the proportion of aUC trial eligibility criteria according to the ASCO-FCR statement. Methods: Protocols indexed on ClinicalTrials.gov with start dates from June 30, 2012 to June 30, 2022 were evaluated. MeSH terms used in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (bladder cancer OR upper tract urothelial carcinoma OR upper tract urothelial cancer)”. International studies enrolling patients aged 18 and over in phases I-III were included. Studies examining multiple cancer types as well as those involving localized treatments (e.g., surgery or ablation), radiation therapy, and prognostic tools were excluded. Analyses of eligibility criteria focused on those highlighted in the ASCO-FCR statement; descriptive statistics were used to define the frequency of eligibility criteria and chi-square and Fisher’s exact test were used to determine their association with treatment type. Results: Overall, 205 urothelial cancer trials were assessed, with 37 (18.0%) having publicly accessible data. Of these, 13 (35.1%) evaluated combination therapy, 11 (29.7%) evaluated immunotherapy, 8 (21.6%) evaluated targeted therapy, and 5 (13.5%) evaluated chemotherapy. HIV positivity, HBV/HCV positivity, brain metastases, and concurrent malignancies were found to be exclusion criteria in 89.2% (33/37), 56.8% (21/37), 35.1% (13/37), and 5.4% (2/37) of studies, respectively. While brain metastases, concurrent malignancies, and HBV/HCV positivity were found to be independent of the class of therapy, a statistically significant association was observed with HIV positivity. Specifically, trials evaluating combination therapy (100.0%), immunotherapy (100.0%) and targeted therapy (87.5%) more frequently included HIV positivity as an exclusion criterion as compared to chemotherapy trials (40.0%). Conclusions: A modest percentage of a UC studies from the last decade were observed to report overly restrictive eligibility criteria as defined by the ASCO-FCR statement. HIV positivity and HBV/HCV positivity were commonly identified exclusion criteria, despite limited evidence that these criteria significantly impact drug efficacy and tolerability. Reassessing and updating eligibility criteria will ensure that the resulting data is more reflective and inclusive of a real-world population.

165 Background: Small cell/neuroendocrine cancers irrespective of origin share aggressive phenotypes. Pembrolizumab (MK-3475) is a humanized antibody targeting programmed cell death protein 1 (PD-1) that has shown activity against small cell lung cancers. Preclinical studies showed molecular commonality amongst small cell cancers across multiple tissue types. This study evaluated the safety and efficacy signals of pembrolizumab and chemotherapy in patients with small cell/neuroendocrine cancer of the prostate and urothelium. Methods: Patients with locally advanced or metastatic small cell cancer of the bladder (cohort 1) and primary small cell or treatment-derived neuroendocrine prostate cancer (NEPC) (cohort 2) received pembrolizumab and standard of care chemotherapy (etoposide and cisplatin/carboplatin for cohorts 1 and 2, with option of docetaxel and carboplatin for cohort 2) with maintenance pembrolizumab for 2 years until unequivocal progressive disease or unacceptable toxicity. Primary endpoint was to estimate ORR, PFS, and OS compared to historical controls as well as safety and tolerability. Targeted gene mutation sequencing as well as sequential single cell sequencing of peripheral blood mononuclear cells (PBMCs) for immune profiling as well T cell receptor (TCR) repertoire was performed. Results: 14 patients were enrolled (7 cohort 1, 7 cohort 2) with mean age 64.9 (range 53 to 81). ORR was 43% (95% CI: 0.06, 0.80) overall and within each cohort. PFS rate at 12 months was 64% (95% CI: 0.44,0.95) across cohorts, 86% (95% CI: 0.63,1.00) within cohort 1, and 43% (95% CI: 0.18,1.00) within cohort 2. OS rate at 12 months was 79% (95% CI: 0.60,1.00) across cohorts, 86% (95% CI: 0.63,1.00) within cohort 1, and 71% (95% CI: 0.45,1.00) within cohort 2. 4 patients in cohort 1 with locally advanced disease underwent radical cystectomy, with no PD at a mean follow up of 29 months. Grade 3 or higher AEs occurred in 87% of patients, while 40% of patients experienced grade 3 or higher AEs related to pembrolizumab. In 12 patients where tissue was sufficient, all patients had genomic alterations in either p53 (75%) or Rb (58%). Single cell sequencing showed progressive enrichment of CD8+ T cells with clonal expansion of specific TCRs in responding patients. Conclusions: In patients with locally advanced or metastatic small cell/neuroendocrine prostate and bladder cancers, combination pembrolizumab with standard of care chemotherapy and maintenance pembrolizumab showed promising efficacy with tolerable adverse events. Clinical trial information: NCT03582475 .

Purpose: Glutaminase is a key enzyme, which supports elevated dependency of tumors on glutamine-dependent biosynthesis of metabolic intermediates. Dual targeting of glucose and glutamine metabolism by the mTOR inhibitor everolimus plus the oral glutaminase inhibitor telaglenastat showed preclinical synergistic anticancer effects, which translated to encouraging safety and efficacy findings in a phase I trial of 2L+ renal cell carcinoma (RCC). This study evaluated telaglenastat plus everolimus (TelaE) versus placebo plus everolimus (PboE) in patients with advanced/metastatic RCC (mRCC) in the 3L+ setting (NCT03163667). Patients and Methods: Eligible patients with mRCC, previously treated with at least two prior lines of therapy [including ≥1 VEGFR-targeted tyrosine kinase inhibitor (TKI)] were randomized 2:1 to receive E, plus Tela or Pbo, until disease progression or unacceptable toxicity. Primary endpoint was investigator-assessed progression-free survival (PFS; one-sided α Results: Sixty-nine patients were randomized (46 TelaE, 23 PboE). Patients had a median three prior lines of therapy, including TKIs (100%) and checkpoint inhibitors (88%). At median follow-up of 7.5 months, median PFS was 3.8 months for TelaE versus 1.9 months for PboE [HR, 0.64; 95% confidence interval (CI), 0.34–1.20; one-sided P = 0.079]. One TelaE patient had a partial response and 26 had stable disease (SD). Eleven patients on PboE had SD. Treatment-emergent adverse events included fatigue, anemia, cough, dyspnea, elevated serum creatinine, and diarrhea; grade 3 to 4 events occurred in 74% TelaE patients versus 61% PboE. Conclusions: TelaE was well tolerated and improved PFS versus PboE in patients with mRCC previously treated with TKIs and checkpoint inhibitors.

OBJECTIVE. The purpose of the present study is to evaluate the diagnostic performance of and interreader agreement for CT colonography (CTC) in the local staging of colon cancer, with emphasis given to the FOxTROT (Fluoropyrimidine, Oxaliplatin, and Targeted-Receptor pre-Operative Therapy [Panitumumab]) trial inclusion criteria, which propose a new tailored treatment paradigm for colon cancer that uses neoadjuvant therapy for patients with a high-risk of locoregional disease as determined by imaging. MATERIALS AND METHODS. This biinstitutional retrospective study involved 89 patients (with 93 tumors) who had colon cancer and underwent presurgical CTC. Two radiologists reviewed the CTC studies for local staging, including measurement of the tumor beyond the muscularis propria on a true orthogonal plane. Histopathologic findings for surgical colectomy specimens served as the reference standard for local pathologic staging. The sensitivity, specificity, positive predictive value, and negative predictive value for local determination of the T category, N category, and extramural vascular invasion (EMVI) were calculated separately for each reader. High-risk T category tumors were the same as those as used in the FOxTROT trial. Interreader agreement was assessed using the kappa statistic. RESULTS. Thirty-five of 93 tumors (37.6%) were histologically classified as high-risk tumors (T3c, T3d, or T4 tumors). The interreader agreement was substantial (κ = 0.68) for classifying high-risk tumors with the use of CTC, moderate for differentiating N0 from N1 and N2 (κ = 0.44), and slight for detecting EMVI (κ = 0.15). The diagnostic statistics for CTC for the two readers were as follows: for detection of high-risk tumors, sensitivity was 65.7% and 82.9%, and specificity was 81.0% and 87.9%; for detection of N category–positive disease, sensitivity was 50.9% and 69.8%, and specificity was 50.0% and 72.5%; and for detection of EMVI, sensitivity was 18.2% and 66.7%, and specificity was 60.0% and 91.7%. CONCLUSION. The present study shows that CTC might be a feasible imaging modality for preoperative local staging of higher-risk colon cancers for which neoadjuvant chemotherapy is more suitable on the basis of the FOxTROT trial criteria. However, further studies are required to allow a better generalization of our results.

510 Background: Small cell/neuroendocrine cancers irrespective of origin share aggressive phenotypes. Pembrolizumab (MK-3475) is a humanized antibody targeting programmed cell death protein 1 (PD-1) that has shown activity against small cell lung cancers. Preclinical studies showed molecular commonality amongst small cell/neuroendocrine cancers across multiple tissue types. This study evaluated the safety and efficacy signals of pembrolizumab and chemotherapy in patients with small cell/neuroendocrine cancer of the prostate and urothelium. Methods: Patients with locally advanced or metastatic small cell cancer of the bladder or upper urinary tract (cohort 1) and primary small cell or treatment-derived neuroendocrine prostate cancer (NEPC) (cohort 2) received pembrolizumab and standard of care chemotherapy (etoposide and cisplatin/carboplatin for cohorts 1 and 2, with option of docetaxel and carboplatin for cohort 2) with maintenance pembrolizumab for 2 years until unequivocal progressive disease or unacceptable toxicity. The primary endpoint was to estimate ORR and PFS compared to historical controls as well as safety and tolerability. Pretreatment targeted gene mutation sequencing was performed. Results: 14 patients were enrolled (7 cohort 1, 7 cohort 2) with mean age 64.9 (range 53 to 81). ORR across cohorts was 43% (95% CI: (0.17, 0.69)), and 43% (95% CI: (0.06, 0.80)) within each cohort. PFS rate at 12 months (proportion of patients who have not progressed at 12 month) was 61% (95% CI: (0.40,0.95)) across cohorts, 86% (95% CI: (0.63,1.00)) within cohort 1, and 36% (95% CI: (0.12,1.00)) within cohort 2. 3 patients in cohort 1 with locally advanced disease exhibited SD and underwent radical cystectomy, with one patient pT0 and no PD at a mean follow up of 20 months. Grade 3 or higher AEs occurred in 71% of patients, while 29% of patients experienced grade 3 or higher AEs related to pembrolizumab. No patients died or discontinued therapy secondary to adverse treatment effects. In 12 patients where tissue was sufficient, all patients had genomic alterations in either p53 (75%) or Rb (58%). Of the 5 available patients with NEPC, 60% had alternations in DNA damage response genes. Conclusions: In patients with locally advanced or metastatic small cell/neuroendocrine prostate and bladder cancers, combination pembrolizumab with standard of care chemotherapy and maintenance pembrolizumab showed promising efficacy with tolerable adverse events. Clinical trial information: NCT03582475.

517 Background: Many patients with muscle-invasive bladder cancer are not ideal candidates for chemotherapy or radical cystectomy. Moreover, local progression may further impair quality of life. Bladder preservation with maximal transurethral resection of bladder tumor (TURBT) and stereotactic body radiotherapy (SBRT) is a viable treatment option for such patients, offering durable local control while potentiating the effect of immunotherapy. Herein, we report on the safety profile of SBRT in combination with durvalumab (anti-PDL1) and tremelimumab (anti-CTLA4) in the safety lead-in cohort of an institutional Phase II trial for cisplatin-ineligible, unresectable locally advanced or metastatic bladder cancer patients. Methods: Patients with locally advanced or metastatic urothelial carcinoma, who were unwilling or unable to undergo radical cystectomy and/or systemic chemotherapy were eligible. Patients received maximal TURBT, followed by durvalumab 1500mg IV every 4 weeks and bladder SBRT 33Gy in 5 fractions between the first 2 cycles. After 6 such patients did not experience a dose limiting toxicity, tremelimumab 75mg IV was added for cycles 1-2. Patients were followed with CT Chest/Abdomen/Pelvis and cystoscopy every 3 months. Treatment-related adverse events (TRAEs) were assessed per CTCAE 5.0 and progression was assessed per RECIST 1.1. Results: Between January 2019 and May 2020, 10 patients received TURBT followed by SBRT and durvalumab (Age 73-96, 3 Female, 7 ECOG 1, 3 ECOG 0). Five patients had localized disease and 5 had nodal or distant metastases. Median cycles of durvalumab was 12.5 (2-13), and 4 patients received 2 cycles of tremelimumab. At a median follow-up of 16.8mo (6.4-30mo), there were 2 Grade 3+ immunotherapy-related TRAEs (1 Grade 3 lipase elevation self-resolved, 2 Grade 3 myositis treated with steroids). The most common TRAEs of any grade included pancreatic enzyme elevation (3 patients), rash (3 patients), and urinary symptoms related to RT (3 patients). Disease control rate 70% and local control was 90%. There were 3 non-treatment related deaths. Conclusions: Bladder SBRT with durvalumab and tremelimumab was well tolerated and demonstrated promising local control in the safety lead-in cohort. Clinical trial information: NCT03601455.

Lipomas are uncommon tumors of the gastrointestinal tract; gastric lipomas account for1% of all gastric tumors encountered (Nickloes and Sutphin [1]). Giant gastric lipomas, defined as ≥10 cm, are exceedingly rare with only 6 cases reported since 1980 (Cappell et al., Termos et al., Singh et al., Ramaraj et al., Rao et al., Priyadarshi et al., Neto et al. [3-9]). We hereby present a case of a giant gastric lipoma that became symptomatic seven years after its initial identification and was excised preserving gastric continuity.Our patient is a 58-year-old African American male with a 3 cm gastric mass incidentally found on CT in 2010. In September of 2017, the patient presented with severe epigastric pain, nausea, and vomiting. Abdominal CT scan revealed an increase in size of the patient's gastric lesion to 7.2 × 10.3 × 7.3 cm. He underwent an exploratory laparotomy with transverse anterior gastrotomy and primary closure. Pathologic examination revealed a 12 cm submucosal, well-circumscribed, non-encapsulated mass comprised of mature adipose tissue without atypia or mitotic figures, consistent with lipoma.The majority of gastric lipomas are asymptomatic, identified on CT scan as round/ovoid masses with low attenuation and homogenous appearance, measuring -80 to -120 Hounsfield units. These findings are nearly pathognomonic. Due to the benign nature of gastric lipomas, circumferential excision with a clear margin of normal tissue is adequate for symptomatic resection. This is the second report of giant gastric lipoma excised with continuity preserving partial gastrectomy, avoiding gastrojejunostomy complications.Fatty tumors are rare in the gastrointestinal tract, yet lipomas must be on the differential when masses are found with Hounsfield units similar to peripheral fat.

Solid organ transplant recipients are at increased risk for developing malignancies. Polyomaviruses (PV) have been historically associated with experimental tumor development and recently described in association with renourinary malignancies in transplant patients. The aim of this study was to investigate the relationship between PV replication and smoking, and the development of malignant neoplasms in kidney transplant recipients.A retrospective case-control study was conducted for PV replication in all kidney biopsies and urine cytologies performed between 1998 and 2014 from kidney transplant recipients at the University of Maryland Medical Center. Polyomavirus-positive patients (n = 943) were defined as having any of the following: a kidney biopsy with PV associated nephropathy, any urine cytology demonstrating "decoy" cells, and/or significant polyomavirus BK viremia. Polyomavirus-negative matched patients (n = 943) were defined as lacking any evidence of PV replication. The incidence of malignancy (excluding nonmelanoma skin tumors) was determined in these 1886 patients and correlated with demographic data and history of smoking.There was a 7.9% incidence of malignant tumors after a mean posttransplant follow-up of 7.9 ± 5.4 years. Among all cancer subtypes, only bladder carcinoma was significantly associated with PV replication. By multivariate analysis, only PV replication and smoking independently increased the risk of bladder cancer, relative risk, 11.7 (P = 0.0013) and 5.6 (P = 0.0053), respectively.The findings in the current study indicate that kidney transplant recipients with PV replication and smoking are at particular risk to develop bladder carcinomas and support the need for long-term cancer surveillance in these patients.

Background Racial outcome disparities have been observed in head and neck squamous cell carcinoma (HNSCC) with diminished survival for black patients compared with white patients. Methods We retrospectively analyzed 1318 patients with primary HNSCC treated at the University of Maryland Greenebaum Cancer Center (UMGCC) from 2000 to 2010. Results Of all the patients, 65.9% were white, 30.7% were black, and 3.3% were of other races. Black patients were less likely to present with oral cavity cancer, and more likely to present with laryngeal or hypopharyngeal cancers. White patients were more likely to have early stage disease, especially in the oral cavity. Black race was independently associated with worse overall survival (OS) in the entire cohort. Black patients had a significantly worse OS among oral cavity and oropharyngeal cancers, with the largest disparity in oropharyngeal cancer. However, in multivariate analysis, race was only still significant in oropharyngeal cancer. Conclusion We observed differences by race in distribution of disease site, stage, and OS. Survival disparity in the entire cohort was driven mostly by differences among oropharyngeal cancer.

There are few studies addressing survival of diffuse peritoneal mesotheliomas (DPM).In this study, survival data were obtained retrospectively from 73 patients treated with intended cytoreductive surgery for DPM, with a mean follow-up of 42 months. Mesotheliomas were classified as well differentiated papillary (WDPM, n = 2), multicystic (MCM, n = 4), and epithelioid mesotheliomas were subclassified as tubulopapillary (TPM, n = 27), solid/deciduoid (S/DM, n = 34), and or biphasic mesothelioma (BPM, n = 6). Invasion was characterised as absent (grade 0), into stroma (grade 1), into fat (grade 2), and into adjacent structures (grade 3). Peritoneal cancer index (PCI) and completeness of cytoreduction (CCR) were assessed surgically.There were no deaths in the WDPM, MCM, and epithelioid DPM with ≤ grade 1 invasion. There was a stepwise decrease in overall survival from invasive TPM, S/DM, and BPM (p 0.0001). By univariate analysis, advanced age (p = 0.01), incomplete CCR (p 0.001), PCI (p = 0.004), mitotic count (p 0.001), nuclear grade (p 0.0001), stromal inflammation (p = 0.013), depth of invasion (p 0.0001), necrosis (p = 0.002), and sarcomatoid growth (p 0.0001) were associated with decreased overall survival. By multivariate analysis, only sarcomatoid growth (p = 0.0006), depth of invasion (p = 0.02), elevated CCR (CCR 2-3) (p = 0.02), and presence of inflammatory stroma (p = 0.04) were significant variables associated with decreased overall survival.DPM form a spectrum of indolent to highly aggressive tumours. Solid epithelioid/deciduoid tumours have a prognosis intermediate between biphasic mesotheliomas and invasive TPM. The presence and degree of invasion, sarcomatoid features, and inflammatory stroma are poor prognostic indicators.