bluuebunny/crossref_metadata_2025 huggingface dataset:
E-cigarette use and the risk of bladder and lung cancer.
Authors: Herriges Michael Joseph , Pinkhasov Ruben , Shapiro Oleg , Jacob Joseph M , Basnet Alina , Bratslavsky Gennady , Goldberg Hanan
Published: February 2022

443

Background: Electronic cigarette smoking and similar novel smoking modalities have raised questions about their impact on various cancers compared with traditional forms of tobacco smoking. Tobacco smoking has been concretely proven to increase the risk of many cancers, including lung (LCa) and bladder (BCa) cancer. To date, there is little data on how e-cigarette smoking impacts the incidence of these cancers. We investigated whether any disparities exist in the prevalence of LCa and BCa between various smoking histories using a US nationally representative data source. Methods: This cross-sectional survey-based US study included men and women aged 18+ from the National Health Interview Survey (NHIS) database between 2016-2018. Primary endpoint was self-reported occurrence of LCa and BCa diagnosis. Multivariable logistic regression analyses assessed possible association of various covariates with diagnosis of these cancers. Results: Prevalence of BCa and LCa was higher in all smoking histories compared to never smokers. Patients with a history of e-cigarette smoking vs. no history of e-cigarette smoking were significantly younger at BCa diagnosis (56.87 [±9.86] vs. 65.00 [±12.60] years, p=0.001). Multivariable logistic regression models showed that a history of cigarette smoking and e-cigarette smoking individually was associated with increased ORs of 2.476 (p≤0.001) and 1.577 (p≤0.001) for BCa diagnosis, respectively, and 4.589 (p≤0.001) and 1.614 (p=0.007) for LCa diagnosis, respectively. Conclusions: Compared to never smokers, history of e-cigarette smoking was associated with increased risk of LCa and BCa development and earlier BCa diagnosis. Additional studies are needed to better define the public health effects of these novel and unregulated products.
The association of FDG PET/CT and NaF PET/CT with survival outcomes in patients (pts) with metastatic genitourinary malignancies (mGU) treated with cabozantinib + nivolumab +/- ipilimumab (CaboNivo +/- Ipi).
Authors: Simon Nicholas I. , Lei Katherine , Verdini Nicholas Peter , Lin Jeffrey , Vega Andy , Niglio Scot Anthony , Mortazavi Amir , Pal Sumanta K. , Kempf Jeffrey , Becker Murray , Knopp Michael V. , Wright Chadwick , Jung Alex , Choyke Peter L. , Steinberg Seth M. , Mena Esther , Lindenberg Liza , Apolo Andrea B.
Published: February 2022

452

Background: This study determined the association of functional imaging parameters obtained on FDG PET/CT and NaF PET/CT with OS for pts with mGU malignancies treated on a phase I study with CaboNivo +/- Ipi. Methods: Pts on this phase I study underwent sequential (1-hour apart) FDG PET/CT and NaF PET/CT imaging at baseline and at first-restaging (8 weeks follow up). Scan semi-quantitative parameters measures included: maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for FDG and MTV for NaF. Total lesion number was captured for all scans. The association of imaging parameters and survival was determined with Kaplan-Meier curves. Baseline values and percent change values were calculated. Results: 81 pts were included in the analysis. 67 (83%) were males; Median age was 63 (range 25-86); Histologically, 30 pts had urothelial carcinoma, 15 clear cell renal cell carcinoma, 9 germ cell tumors, 8 urachal/adenocarcinoma, 8 prostate cancer, 3 penile cancer, 3 squamous cell carcinoma, 3 renal medullary carcinoma, and 2 small cell (1 bladder, 1 prostate). All 81 had a baseline FDG PET scan, 78 pts received baseline NaF PET scans; 66 received both FDG PET and NaF PET baseline and follow up scans. 957 total lesions were detected on FDG PET across all histologies, 87 liver (9%), 252 lung (26%), 152 bone (16%), 411 lymph node (43%), and 55 other visceral metastases (6%). 414 total lesions were detected on NaF imaging. Low vs high baseline FDG MTV (31 vs 11 months, p = 0.0002), TLG (30 vs 11 months, p = 0.0004), Lesion number (49 vs 15 months, p = 0.0005), and SUVmax (25 vs 12 months, p = 0.025), FDG lesion number decrease or no change vs increase (24 vs 12 months, p = 0.0068), and low vs high baseline NaF MTV (26 vs 16 months, p = 0.007), and lesion number (26 vs 16 months, p = 0.007) showed the strongest associations with OS. A multivariable Cox analysis demonstrated that baseline FDG MTV (HR = 2.87, 95% CI 1.62-5.08, p = 0.0003) and FDG lesion number percent change (HR = 2.71, 95% CI 1.40-5.24, p = 0.0031) were jointly associated with OS. Conclusions: Baseline functional imaging parameters and percent change seen on follow imaging with FDG PET and NaF PET are prognostic in mGU pts treated with CaboNivo +/- ipi. Additional parameters and histologic subsets will be presented.
Criteria used to determine platinum eligibility and first-line (1L) treatment (tx) patterns among platinum-eligible (PE) and -ineligible (PI) patients (pts) with metastatic urothelial cancer (mUC) in France, Germany, Spain, Italy, and the United Kingdom (Eu5).
Authors: Milloy Neil , Kirker Melissa , Berry Mia , Kostikas Michael , Montgomery Rachel , Kearney Mairead , Costa Nuno Matos , Chang Jane
Published: February 2022

457

Background: European Society for Medical Oncology (ESMO) guidelines recommend tx for mUC based on cisplatin and platinum eligibility. To date, most real-world analyses have not included physician-confirmed eligibility status. This study collected mUC patient data in Eu5 and summarized the criteria used in the real-world setting to determine PE and 1L tx prescribed based on PE. Methods: Data were drawn from the Adelphi mUC Disease-Specific Programme, a real-world point-in-time study conducted from November 2020 to April 2021. Oncologists and urologists were enrolled in the study and recruited the next 8 eligible pts who came for a consultation. Demographic, clinical characteristics, platinum eligibility, and tx patterns were collected. Results: Physicians provided data on 1,868 mUC pts who were receiving or had completed 1L tx and had a known PE status as determined by a physician prior to 1L tx. Renal function contributed to physicians’ platinum eligibility decisions for 72% of pts; ECOG score and age were used in 59% and 38% of pts, respectively. The mean (SD) age was 69.1 (7.88) years and 73% were men. At initial mUC diagnosis (dx), 25% were PD-L1–positive, 17% were PD-L1–negative, and 58% had either unknown PD-L1 status or were not tested. 87% of pts were PE (55% were eligible for cisplatin and carboplatin; 31% were cisplatin ineligible), and 13% were PI. PE pts who were eligible for cisplatin and carboplatin were younger than cisplatin ineligible and PI pts (66.6, 71.9 and 73.1 years, respectively). The percentage of pts with ECOG 0 or 1 at dx was 92%, 79%, and 67% for cisplatin and carboplatin eligible, cisplatin ineligible, and PI pts respectively. Conclusions: Only a small proportion of pts were classified as PI. The majority of PE pts received guideline-recommended tx with platinum-based regimens in the 1L. Overall, there was limited use of immune checkpoint inhibitor tx in the 1L, with use observed primarily among PI pts. Some guideline deviations were observed, including pts deemed PI who still received platinum-based chemotherapy. Recently, ESMO guidelines were updated to include avelumab for 1L maintenance tx in PE pts. Future studies should evaluate concordance with updated guideline recommendations in PE pts and rationale for guideline deviations.[Table: see text]
Impact of COVID-19 on cancer caregivers: Results from the Global Carer Well-being Index.
Authors: Turpin Karen V.L. , Foland Elizabeth , Patton Taylor , Guterl Jeremy , Zapakin Marni , Greenamyer Jasmine
Published: February 2022

460

Background: Caregiver burden has been intensified by the COVID-19 pandemic. The Carer Well-being Index is a global research study commissioned by Embracing Carers, a partnered initiative with nine global caregiving organizations. The study sought to explore and delineate the impact of the pandemic on the health and well-being of caregivers across the globe, including those caring for persons with cancer. Methods: The survey was conducted via online and phone methodologies in September and October 2020, with over 9,000 unpaid carers across 12 countries, including the United States and Canada. Unpaid carers were defined as those who care for someone with a long-term illness (e.g., cancer), physical disability (e.g., spinal cord injury), or cognitive/mental condition (e.g., Alzheimer’s). The base sample size for cancer caregivers from the global surveyed population was n=1035. Statistically significant differences between cancer carers and non-cancer carers were evaluated using the Chi-square test with p ≤ 0.05. Results: 63% of all caregivers were women, with a 60/40 female to male split in the cancer carer group. While the average age of started caregiving was 37.2 years, and 39.0 in cancer carers, caregivers caring for someone with cancer were more likely than the average caregiver to be in the 60+ age group. Compared to non-cancer caregivers surveyed, a higher percentage of cancer caregivers became carers in the last year (26 vs 13% of non-cancer caregivers). Providing emotional support, managing doctor appointments, preparing meals, home maintenance and housekeeping, transportation, and giving/managing medications were more likely to be among cancer caregivers' primary responsibilities, compared to non-cancer caregivers. Cancer carers were significantly more likely than non-cancer carers to have reported negative impacts because of COVID on their emotional/mental, physical, and financial health, and paid work responsibilities. Overall, cancer caregivers were significantly more likely to report that COVID has made caregiving harder than non-cancer caregivers (71 vs 63%), and were more likely to report never receiving support from a variety of organizations, such as insurance organizations (71 vs. 66% non-cancer caregivers) and local/state government (73 vs. 66%). Of note, cancer carers were more likely to report a positive impact on the relationship with the person being cared for (61 vs. 56%). Conclusions: These results highlight the burdens that have been intensified for cancer carers. Actions are needed to help with health and well-being such as offering and promoting mental health services, respite care; providing financial support to take leaves from paid work, access to equipment and services such as housecleaning. By working together with health care providers, organizations, and government on these types of initiatives, the burden upon cancer caregivers can be lessened.
Changes in body composition during neoadjuvant platinum-based chemotherapy associations prior to radical cystectomy: Implications for chemotherapy-associated adverse events and oncologic outcomes.
Authors: Maldonado Reno , Fintelmann Florian J. , Marquardt Jan Peter , O'Malley Ryan Blair , Holt Sarah K. , Ngo Steven , Diamantopoulos Leonidas Nikolaos , Laidlaw Grace , Schade George R. , Lin Daniel W. , Wright Jonathan L. , Gore John L. , Nyame Yaw A. , Grivas Petros , Yu Evan Y. , Montgomery Robert B. , Hsieh Andrew Caleb , Yezefski Todd , Schweizer Michael Thomas , Psutka Sarah P.
Published: February 2022

476

Background: Low skeletal muscle index (SMI) is associated with an increased risk of mortality in muscle-invasive bladder cancer (MIBC) and chemotherapy-related adverse events (AE) across numerous other malignancies. Small case series suggest neoadjuvant chemotherapy (NAC) is associated with a significant decline in SMI in patients with MIBC. However, limited data exists regarding changes in fat mass during NAC. Herein, we examine changes in SMI, visceral fat index (VFI), and subcutaneous fat index (SFI) in patients receiving NAC for MIBC before radical cystectomy (RC). We describe associations between body composition changes and NAC-associated AE and all-cause mortality (ACM) in patients with MIBC. Methods: Retrospective review of patients with MIBC (≥pT2 N0/x/1 M0) who received NAC (2006-2019). Patients with digitized abdominal computed tomography scans (CT) within 75 days prior (T1) and 75 days following completion (T2) of NAC were included. We segmented and calculated the indices (cm2/m2) for SMI, VFI, and SFI at the third lumbar vertebra level at T1 and T2 using validated methodology. Associations with AE during NAC and ACM were evaluated with multivariate logistic regression and Cox proportional hazards models. Results: Included 170 patients, median age 63 years receiving a median of 4 (IQR 3-5) cycles of Gemcitabine/Cisplatin (52%), MVAC (28%), or other NAC (20%). Absolute and relative changes in SMI, VFI, and SFI over a median of 112 days (IQR 94-146) between measurements are presented in the Table. 117 (69%) patients experienced grade ≥3 chemotherapy-related AE. No associations between baseline body composition or change in body composition during NAC with chemotherapy-related AE. T1 SMI (HR: 0.98; 0.97-0.99, p = 0.008), as well as T2 SMI (HR: 0.98; 0.96-0.99, p = 0.003), T2 VFI (HR: 0.99; 0.99-1.0, p = 0.05) and T2 SFI (HR: 0.99; 0.98-1.0, P = 0.03) were associated with ACM after adjusting for age, clinical T and N stage, and performance status. Conclusions: Patients undergoing NAC prior to RC experienced a 6.4% decrease in SMI and a 5.2% decrease in VFI during an average of 112 days. Chemotherapy-related AE were not associated with a change in body composition. Baseline SMI and T2 SMI, SFI, and VFI were associated with ACM on multivariable analysis. Future work is needed to understand the mechanisms underpinning such changes and the extent to which potentially detrimental changes in body composition may be mitigated before surgery.[Table: see text]
Phase I-II study to evaluate safety and efficacy of niraparib plus cabozantinib in patients with advanced urothelial/kidney cancer (NICARAGUA trial): Preliminary data of phase I study.
Authors: Castellano Daniel E. , Duran Ignacio , Mellado Begona , Climent Duran Miguel Angel A. , Garcia del Muro Xavier , Sala González Nuria , Alonso Gordoa Teresa , Sevillano Elena , Domenech Montserrat , Paramio Jesus , Real Francisco X. , Malats Nuria , Sanz Juan Luis , Font Albert ,   Fundación CRIS
Published: February 2022

490

Background: Niraparib (N) is a (PARP)-1/-2 inhibitor and Cabozantinib (C) is a tyrosine kinase (TK) inhibitor that targets VEGF signalling via inhibition of multiple TK receptors including c-MET and TAM kinases (TYRO3, AXL, MER). The c-Met receptor TK is abnormally activated and could be decrease response to PARP inhibitors. Preclinical data reveals that treatment with c-Met inhibitors renders cells more sensitive to PARP inhibition. A phase (Ph) I-II study was designed to explore the safety and efficacy of the combination of N + C in genitourinary cancers. Methods: Multicenter, open-label Ph I-II study (NCT03425201). Confirmed histopathological diagnosis of either metastatic urothelial carcinoma (mUC) or advanced clear cell renal cell carcinoma previously treated with a maximum of two previous regimens. Adequate bone marrow, liver and renal functions were required. The Ph I portion aimed to identify the maximum tolerated dose (MTD) and recommended ph II dose (RP2D). Pt received N and C p.o. once daily in 28-day cycles: Dose level 1 (DL1) N/C 100/20 mg; DL2 200/20 mg; DL3 200/40 mg; DL4 200/60 mg. A further amendment developed DL1.1 100/40 mg. Pt were accrued to each dose level in cohorts of 6 pt until the MTD was achieved (defined as highest dose at which ≤1 out of 6 pt experience a DLT, evaluated during the first 2 cycles). Results: Nineteen evaluable pt for DLT were included, 14 of them had UC. There was no DLT at DL1. Two out of the first 6 evaluable pt in DL2 had DLT (G3 thrombopenia and anemia and G3 diarrhea respectively). Upon analysis of these pt it was agreed to include 3 additional new pt for evaluation. Two pt were included with one presenting a DLT (G3 hepatic toxicity). Enrolment then continued in a new DL 1.1 cohort and 1 of 6 pts had DLT (G3 mucositis), being then considered the RP2D. No toxic deaths were reported. Six pt (32%) received at least 10 cycles and 9 pt (47%) received at least 6 cycles. Three patients (16%) achieved partial response (all of them with mUC disease) and 14 (74%) stable disease. Conclusions: N plus C combination can be safely administered with a manageable toxicity profile and preliminary efficacy was reported in mUC heavily pretreated pts. The RP2D is N 100 mg plus C 40 mg qd. Ph II study is now recruiting mUC patients. Clinical trial information: NCT03425201. [Table: see text]
Gemcitabine and carboplatin versus gemcitabine and paclitaxel chemotherapy in cisplatin ineligible advanced-stage urothelial cancers: A prospective randomized control study.
Authors: Kumar Parmod , Sehrawat Amit , sundriyal Deepak , Sharma Pankaj , Mittal Ankur , Gupta Manoj Kumar
Published: February 2022

500

Background: Cisplatin ineligibility in metastatic urinary bladder cancer patients poses a major therapeutic challenge. The reported incidence was approximately 20-30% of metastatic urinary bladder cancer. In the absence of insurance, "the immunotherapy" can be economically draining at the current cost. Moreover, there are patients in whom immunotherapy might not be feasible due to comorbid conditions. Therefore, there persists a need to optimize chemotherapy options for gemcitabine combination with either Paclitaxel or Carboplatin are recommended chemotherapy options. However, limited prospective studies are comparing the two options. Methods: This was a non-funded, prospective, randomized, single-center study among treatment naïve cisplatin-ineligible metastatic urothelial cancer from a tertiary care institute from India. The study enrollment duration was 18 months. Patients were randomized in one of the two treatment arms. The "Arm A" received (Gemcitabine and Carboplatin) and "Arm B" received the (Gemcitabine and Paclitaxel) combination chemotherapy, respectively. The two treatment arms were compared prospectively for disease control, survival, and adverse events in an Intention to treat analysis. Results: A total of 32 eligible participants were randomized in the study. "Arm A" vs. "Arm B" had an 18.7% vs. 25% drops out rate, respectively. The ORR was 40% vs. 88.4%; median PFS and OS were 3.7 vs. 3.8 months and 7.3 vs. 14.0 months, respectively. The serious adverse events were nonoverlapping. Hospitalization was needed for the care of adverse events among 37.5% vs. 12.5% patients, respectively. Conclusions: Both groups reported that similar PFS. However, better ORR, OS (though not statically significant), and lower hospitalizations for adverse event management favor the Gemcitabine with paclitaxel combination over Gemcitabine with Carboplatin. Clinical trial information: CTRI/2020/02/023402.
Targeting urothelial neoplasia using an investigational virus-like drug conjugate.
Authors: Kines Rhonda , Railkar Reema S. , Agarwal Piyush K. , Schiller John T
Published: February 2022

514

Background: Human papillomavirus virus-like particles (HPV VLP) preferentially target tumor cells via cell surface modified heparan-sulfate proteoglycans (HSPG). The investigational virus-like drug conjugate, belzupacap sarotalocan (AU-011), is currently in phase 2 clinical trials for treatment of primary choroidal melanoma. We previously demonstrated AU-011’s in vivo tumor acute cytotoxicity upon activation with near-infrared light (nIR), resulting in tumor-free survival for at least 100 days and protection from tumor re-challenge in the MB49 murine flank model of bladder cancer. Here we provide additional data supporting further clinical development in urothelial neoplasia as an additional oncology indication. Methods: We examined the cytotoxicity of AU-011 in a panel of six human bladder cancer cell lines in vitro and binding and distribution in human tumor biopsy samples ex vivo. Tumor distribution of AU-011 was also assessed in vivo after intravesical instillation in the orthotopic MB49 murine model. In consideration of the glycocalyx layer often found coating the interior of the bladder wall and the surface of bladder tumors, pre-treatment with hyauronidase was tested both on human biopsy samples and in the murine orthotopic model. Lastly, tumor distribution of AU-011 was evaluated when formulated with the polyamide Syn3. Results: When tested in vitro on a panel of human bladder tumor cell lines representing grades I-IV carcinomas, we found AU-011’s potency to be in the picomolar range (EC50 range 16.6 pM – 62.75 pM). We assessed the VLPs ability to bind ex vivo to a panel of human urothelial tumor biopsies and observed binding in samples representing both invasive T2 and non-invasive Ta papillary tumors. Tumor biopsy samples were pre-treated with hyaluronidase to break down the glycocalyx layer surrounding the tumor, and an increase in signal was observed in the Ta biopsy sample. Similarly, using the orthotopic MB49 murine tumor model with intravesical delivery of AU-011, we observed an enhancement of AU-011 distribution into the tumor when the bladders were pre-treated with hyaluronidase. Additionally, when formulated with Syn3, AU-011 distribution throughout the tumors was augmented without the need for hyaluronidase pre-treatment. Conclusions: We have demonstrated AU-011 targeted cytotoxicity in vitro using a panel of human bladder cancer cell lines indicating that its binding to bladder cancer cells is tumor grade and genetic mutation agnostic. Additionally, tumor binding and distribution was observed ex vivo using human bladder cancer biopsy samples and in vivo in the murine MB49 orthotopic model. Human and murine tumor distribution was improved with a pre-treatment of hyaluronidase or when formulated with Syn3. Collectively, these data support the further investigation of the use of AU-011 for the indication of uroepithelial cancer.
Characterizing molecular subtypes of high-risk nonmuscle-invasive bladder cancer in African American patients.
Authors: Williams Stephen B. , You Sungyong , Kim Minhyung , Widen Steven G. , Yu Alexander , Eyzaguirre Eduardo J. , Dyrskjøt Lars , McConkey David , Choi Woonyoung , Theodorescu Dan , Chan Keith S. , Shan Yong , Tyler Douglas S. , De Hoedt Amanda M. , Freedland Stephen J.
Published: February 2022

527

Background: Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) have heterogeneous outcomes with African Americans (AAs) having worse survival than European Americans (EAs). It is unknown whether race-based biological differences contribute to this disparity. Methods: We performed a retrospective cohort study including patients from the University of Texas Medical Branch (UTMB) and the Durham VA Health Care System (DVAHCS) from 2010-2020 among treatment naïve, high-risk NMIBC. Profiled gene expressions of high-risk NMIBC by race were performed using the UROMOL classification system. Results: A total of 26 patients (14 AAs and 12 EAs) matched on age and sex were included with no significant difference in clinical stage group (CIS +/- T1 or TaHG vs. TaHG or T1, no CIS), smoking status, or progression. We found a similar racial UROMOL subtype distribution with class 2a being most common. A total of 10 genes were discovered to be commonly upregulated differentially expressed genes (up-DEGs) in AAs vs EAs. EFEMP1, which has been associated with progression to muscle-invasive bladder cancer (MIBC) in vitro, and S100A16 gene expression, which has been implicated with mitomycin C resistance in bladder cancer in vitro, was significantly more common among AAs. We used single nuclei analysis to map the malignant cell heterogeneity in urothelial cancer which five distinct malignant epithelial subtypes whose presence has been associated with different therapeutic response prediction ability. We mapped the expression of the 10 genes commonly up-DEGs by race as a function of the five malignant subtypes. This showed borderline (p = 0.056) differences among the subtypes suggesting AA and EA patients may be expected to have different therapeutic responses to treatments for BC. AAs were enriched with immune-related, inflammatory, and cellular regulation pathways compared to EAs, yet appeared to have reduced levels of the aggressive C3 bladder tumor cell population. Conclusions: In this small sample, we found similar subtype distribution among high-risk NMIBC patients according to race. However, gene expression differs by race, supporting potential novel race-based etiologies for differences in muscle-invasion, response to treatments, and transcriptome pathway regulations. Further biological studies in NMIBC molecular sub-stratification, associated treatment(s), and prognoses in a larger cohort are needed to support these hypotheses.
Biomarkers predictive of response to enfortumab vedotin (EV) treatment in advanced urothelial cancer (aUC).
Authors: Jindal Tanya , Zhang Li , Chou Jonathan , Shui David , Porten Sima P. , Wong Anthony C. , Chan Emily , Stohr Bradley A. , de Kouchkovsky Ivan , Borno Hala , Bose Rohit , Kwon Daniel H , Desai Arpita , Huang Franklin W. , Aggarwal Rahul Raj , Small Eric Jay , Fong Lawrence , Friedlander Terence W. , Koshkin Vadim S
Published: February 2022

531

Background: EV is an antibody-drug conjugate which recently received full FDA approval for treatment-refractory aUC. Molecular biomarkers and characteristics of patients (pts) most likely to respond to EV therapy have not been well defined. Methods: We retrospectively identified all aUC pts treated with EV at our institution. Clinicopathologic, treatment and response data were abstracted from pt charts. Pts were considered responders to EV if they had a complete response on initial scans after 2-3 months of treatment, or were treated with EV for ≥ 6 months. Responders and non-responders were compared in terms of their molecular and clinical characteristics using Chi-squared test. Most common somatic alterations present in ≥10 pts ( TERTp, TP53, CDKN2A, CDKN2B) were also used to divide pts with available next-generation sequencing (NGS) results into groups with and without these alterations. Log rank test was used to determine differences in overall survival (OS) and progression free survival (PFS) among these groups. Results: Between 1/2020 and 8/2021 a total of 32 pts received EV and 28 had NGS data available with either FoundationOne (14 pts), UCSF500 (13 pts) or Strata (1). Median age was 69.5 years, 24 (75%) were male, 22 (69%) Caucasian, 22 (69%) had pure urothelial histology and 22 (69%) primary tumor location in the bladder. At EV start, 24 (75%) had visceral metastases (mets), 8 (25%) had liver mets, and 13 (41%) had bone mets. Median follow-up from EV start was 12.5 months (range 0.5-36); 20 (63%) pts received EV monotherapy, and 12 (37%) received EV as part of a combination regimen. Non-responders were more likely to have bone metastases (69% vs 21%, p<0.01), but were otherwise similar in baseline clinical characteristics to responders. TP53 alterations were enriched in responders relative to non-responders, whereas non-responders had more CDKN2B alterations (Table). Similar findings were seen in the subset of pts treated with EV monotherapy. Pts with TP53 alterations had longer OS (NR vs 17.0 months, p=0.06) and PFS (NR vs 6.6 months, p=0.04) relative to wild-type pts. Shorter PFS was seen in pts with CDKN2A (4.4 months vs NR, p=0.05) and CDKN2B (4.3 months vs NR, p=0.02) alterations, but no differences in OS were observed. Conclusions: In this retrospective cohort of aUC pts with available NGS data, presence of TP53 and absence of CDKN2A and CDKN2B alterations were associated with favorable responses and improved clinical outcomes with EV, suggesting they may be biomarkers of response to EV. These preliminary findings should be validated in larger cohorts.[Table: see text]
A randomized, controlled trial of group exercise training for fall prevention and functional improvements during and after treatment for prostate cancer.
Authors: Winters-Stone Kerri M. , Li Fuzhong , Horak Fay B. , Dieckmann Nathan , Hung Arthur , Amling Christopher L. , Beer Tomasz M.
Published: February 2022

TPS193

Background: Many prostate cancer survivors are treated with androgen deprivation therapy (ADT), but these therapies may increase frailty, worsen physical functioning, and increase fall risk. While exercise may counter functional declines associated with ADT, no studies have tested whether and which type of exercise may reduce falls and frailty. The purpose of this trial is to compare the relative efficacy of strength training versus tai ji quan training against each other and to a stretching control group on falls, frailty and physical functioning in men expose to ADT for prostate cancer. Methods: Prostate cancer survivors treated with ADT (n = 360) will be recruited to participate in this single-blind, parallel group, randomized trial. To be eligible men must meet the following criteria: 1) histologically confirmed prostate cancer, 2) received at least 6 months of ADT within the past 10 years, 3) report >1 fall in the past year OR have a score on one of two physical performance tests that is associated with increased fall risk (i.e. ≥ 12.0 seconds to complete the 3 meter timed up and go (TUG), or ≥ 10.0 seconds to complete 5 chair stands), 4) completed any other treatment at least 6 weeks prior to enrollment and not be on any concurrent prostate cancer therapy besides ADT, 5) not currently participating in moderate-vigorous intensity lower-body strength training or tai ji quan training ≥ 2 times/week for ≥ 30 minutes per session, 6) no cognitive difficulties that limit ability to answer survey questions or participate in exercise classes and performance tests, 7) no medical condition, disorder, or take medication that contraindicates participation in moderate intensity exercise, and 8) are able to communicate in English. Participants will be randomized to one of three supervised, group training programs: i) strength training, ii) tai ji quan training, or iii) stretching (control), that train 3x/week for 6 months. Outcomes are assessed at baseline, 3 (mid-intervention), 6 (immediately post-intervention) and 12 (follow-up) months. The primary outcome is falls assessed by monthly self-report. Secondary outcomes include the following: Frailty (low lean body mass (by bioelectrical impedance analysis), exhaustion (by SF-36 vitality scale), low activity (by CHAMPS physical activity survey), slowness (by 4m usual walk speed), and weakness (by chair stand time)); Objective and subjective measures of physical function will also be collected. Negative binomial regression models will be used to assess differences in falls between groups, while mixed-effects modeling will be used to compare the relative efficacy of training group on secondary outcomes. Registered November 18, 2018. Clinical trial information: NCT03741335.
TiNivo-2: A phase 3, randomized, controlled, multicenter, open-label study to compare tivozanib in combination with nivolumab to tivozanib monotherapy in subjects with renal cell carcinoma who have progressed following one or two lines of therapy where one line has an immune checkpoint inhibitor.
Authors: Choueiri Toni K. , Albiges Laurence , Hammers Hans J. , McKay Rana R. , Heng Daniel Yick Chin , Beckermann Katy , Kasturi Vijay , Motzer Robert J.
Published: February 2022

TPS405

Background: Tivozanib, a highly selective and potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, has demonstrated single-agent efficacy in advanced renal cell carcinoma (aRCC) along with minimal off-target toxicities and a favorable adverse event (AE) profile (Rini et al. Lancet Oncol 2020; 21:95-104). Tivozanib was approved by the FDA on March 10, 2021, for the treatment of patients with aRCC who had progressed on 2 or more prior lines of therapy. Tivozanib was combined with Nivolumab in the TiNivo trial (NCT03136627), showing an objective response rate of 56%, disease control rate of 96%, median PFS of 18.9 months and a favorable safety profile (Albiges et al. Ann Oncol. 2021 Jan;32(1):97-102). Methods: TiNivo-2 (NCT04987203) is a phase 3, randomized, controlled, multicenter, open-label study to compare tivozanib in combination with nivolumab to tivozanib monotherapy in subjects with renal cell carcinoma who have progressed following 1-2 lines of therapy including an immune checkpoint inhibitor. Eligibility criteria include age >18 years, clear cell RCC, ECOG PS 0-1, and disease progression during or following at least 6 weeks of treatment with ICI for RCC. Subjects will be stratified by IMDC risk category and whether ICI was received in most recent line of treatment or not. On both arms, subjects will receive Tivozanib 1.34 mg orally once daily for 21 consecutive days followed by 7 days off. In the combination arm, subjects will also receive Nivolumab 480mg intravenously every 4 weeks. Study assessments include CT scan or MRI of the chest, abdomen, and pelvis every 8 weeks following Cycle 1 Day 1 for 2 years and every 12 weeks thereafter until disease progression is confirmed by independent radiology review. The primary objective is to compare the progression-free survival (PFS) of tivozanib in combination with nivolumab to tivozanib. A sample size of 326 subjects, with 191 events will provide at least 80% power to detect a 50% improvement in PFS, 12 mos v. 8 mos, as assessed by an IRR. Secondary endpoints include assessment of overall survival (OS), objective response rate (ORR), and duration of response (DoR), as well as safety and tolerability. Exploratory endpoints are to assess the quality of life (FKSI-DRS and EORTC QLQ C-30) and to investigate the pharmacokinetics of tivozanib. TiNivo-2 is actively enrolling and planning to open at 190 sites in the United States, and the European Union. Clinical trial information: NCT04987203.
A phase 3, single-arm study of CG0070 in subjects with nonmuscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guerin (BCG).
Authors: Uchio Edward M. , Lamm Donald L. , Shore Neal D. , Kamat Ashish M. , Tyson Mark , Tran Ben , Anderson Paul , Grandi Paola , Burke James M.
Published: February 2022

TPS598

Background: CG0070 is a serotype 5 adenovirus engineered to express GM-CSF and replicate in cells with mutated or deficient RB, with response rates (RR) of approximately 45% observed in patients with recurrent NMIBC after BCG (J Urol. 2012;188:2391–7; Urol Oncol. 2018;36(10):440–7). This single arm phase 3 study (NCT04452591) was launched to confirm the clinical activity of CG0070 in patients with BCG Unresponsive NMIBC. Methods: 110 patients with BCG-unresponsive CIS with or without concurrent Ta or T1 disease will be treated with intravesical (IVe) CG0070 at a dose of 1x1012 vp. CG0070 will be administered as follows: induction weekly x 6 followed by weekly x 3 maintenance instillations at months 3, 6, 9, 12, and 18. Patients with persistent CIS or HG Ta at 3 months (m) may receive re-induction with weekly x 6 CG0070. Assessment of response will include q 3 m cystoscopy with biopsy of areas suspicious for disease, urine cytology, CTU/MRU, and mandatory bladder mapping at 12 m. Detection of high grade disease within the bladder will be enumerated as recurrence or non-response. The primary endpoint of the study is CR at any time on study as assessed by biopsy (directed to cystoscopic abnormalities and mandatory mapping at 12 m), urine cytology, and radiography, as above. Secondary endpoints include CR at 12 m, duration of response, progression free survival, cystectomy free survival and safety. Correlative assessments include changes in the tumor immune microenvironment, systemic immune induction as reflected in the peripheral blood and urine, as well as viral replication and transgene expression. Baseline expression of coxsackie adenovirus receptor, E2F transcription factor as well as anti-adenovirus antibody titer will be correlated with tumor response. Study enrollment globally is ongoing including in North America, Taiwan, Japan, and South Korea. Refs. Burke JM, Lamm DL, Meng MV, Nemunaitis JJ, Stephenson JJ, Arseneau JC, Aimi J, Lerner S, Yeung AW, Kazarian T, Maslyar DJ, McKiernan JM. A first in human phase 1 study of CG0070, a GM-CSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. Clinical trial information: NCT04452591.
Disparities in Guideline-Concordant Treatment and Survival Among Border County Residents With Gastric Cancer
Authors: Ju Michelle R. , Wang Sam C. , Mansour John C. , Polanco Patricio M. , Yopp Adam C. , Zeh Herbert J. , Porembka Matthew R.
Published: February 2022

PURPOSE:

Previous studies have shown health disparities among US-Mexico border county (BC) residents. However, the impact of BC residence on gastric cancer treatment and survival outcomes is unknown. Our study compares the receipt of guideline-concordant care (GCC) and survival for patients with gastric cancer by BC status.

METHODS:

We conducted a retrospective review of adult non-Hispanic White and Hispanic patients with gastric adenocarcinoma diagnosed between 2004 and 2017 in the Texas Cancer Registry. Chi-square tests were used to compare categorical group differences, with pooled t-tests used to compare group means. The impact of BC residence on likelihood of receiving GCC was assessed with logistic regression. Overall survival was estimated using the Kaplan-Meier method and compared with log-rank tests.

RESULTS:

Our cohort consisted of 12,514 patients (15% BC). Overall, 45% of nonborder county residents received GCC versus 35% of BC residents ( P < .0001). After adjusting for age, race, stage, and insurance status, BC patients remained significantly less likely to receive GCC (odds ratio 0.69; 95% CI, 0.61 to 0.78). BC residence was associated with increased hazard of all-cause mortality after accounting for age, race, stage, poverty index, and treatment receipt (hazard ratio 1.11; 95% CI, 1.04 to 1.18). BC residents had significantly worse overall survival for localized and regional disease.

CONCLUSION:

BC residents with gastric cancer are less likely to receive GCC and have significantly worse survival outcomes than nonborder county residents. This highlights significant health care disparities arising from the lack of health care access and multiple social determinants of health. Further studies are needed to identify specific contributing mechanisms to improve health care equity.
Universal patterns in multifrequency-driven dissipative systems
Authors: Olivera-Atencio M. L. , Lamata L. , Kohler S. , Casado-Pascual J.
Published: February 2022

The response of dissipative systems to multi-chromatic fields exhibits generic properties which follow from the discrete time-translation symmetry of each driving component. We derive these properties and illustrate them with paradigmatic examples of classical and quantum dissipative systems. In addition, some computational aspects, in particular a matrix continued-fraction method, are discussed. Moreover, we propose possible implementations with quantum optical settings.
Detecting wetland encroachment and urban agriculture land classification in Uganda using hyper-temporal remote sensing
Authors: Kabiri Stella , Allen Molly , Okuonzia Juduth Toma , Akello Beatrice , Ssabaganzi Rebecca , Mubiru Drake
Published: February 2022

Background: Urbanization is an important indicator of economic growth and social change but is associated with environmental degradation, which threatens the sustainable growth of African cities. One of the most vulnerable ecosystems in urban areas are wetlands. In Uganda, wetlands cover an area of 11% of the country’s land area. Half of the wetland areas in Ugandan cities have been converted to industrial and residential areas, and urban agriculture. There is limited information on the extent of wetland conversion or utilization for urban agriculture. The objective of this study was to investigate the extent of wetlands lost in two Ugandan cities, Wakiso and Kampala, in the last 30 years. Secondly, we extracted crop agriculture in the wetlands of Kampala and Wakiso from hyper-temporal satellite image analysis in an attempt to produce a spatial detail of wetland encroachment maps of urban agriculture using a reproducible mapmaking method.

Methods: Using a field survey and free remote sensing data from Landsat TM 1986 and Landsat ETM 2016 we classified the rate of wetland loss and encroachment between the years 1986 and 2016. We used MODIS NDVI 16-day composites at a 500-meter spatial resolution to broaden the analysis to distinguish distinctive crops and crop mixtures in the encroached wetlands for urban agriculture using the ISODATA clustering algorithm.

Results: Over 30 years, 72,828 ha (73%) of the Wakiso-Kampala wetlands have been lost meanwhile agriculture areas have doubled. Of this 16,488 ha (23%) were converted from wetlands. All cultivated agriculture in Kampala was in the wetlands while in Wakiso, 73% of crop agriculture was in the wetlands. The major crops grown in these urban wetlands were banana (20%), sugarcane (22%), maize (17%), Eucalyptus trees (12%), sweet potatoes (10%), while ornamental nurseries, pine trees, vegetables, and passion fruits were each at 5%.
Case Report: Bocavirus Infection Radiologically Resembling a Congestive Heart Failure in a Patient with Metastatic Castration-Resistant Prostate Cancer Case-Report
Authors: Benitez Fuentes Javier David , de Luna Aguilar Alicia , Flores Navarro Paloma , Lopez de Sa Lorenzo Alfonso , Toledano Rojas Carmen , Laguna Fonseca Berta , Shah Richa , Frick Clara , Jimenez Ortega Alejandro Francisco , Vidal Cassinello Natalia
Published: February 2022

Background: Human bocavirus (HBoV) is a viral pathogen from the genus Bocaparvovirus (family Parvoviridae, subfamily Parvovirinae) discovered in 2005. Most of available literature is about HBoV in children and adults with hematological malignancies and in otherwise healthy children with respiratory infections. Information regarding infection in the adult population with solid tumors is scarce.

Case Report: We report the case of a 51-year-old male with metastatic castration resistant prostate cancer undergoing chemotherapy treatment who presented with fever, dyspnea, dry cough, and pleuritic pain. Imaging techniques showed signs of congestive heart failure. Symptoms, laboratory tests and echocardiography revealed a more probable infectious etiology. Antibiotic therapy was started. A polymerase chain reaction (PCR) test of nasopharyngeal exudate for respiratory viruses was positive for HBoV. The rest of the microbiological tests were negative. Bronchoalveolar lavage (BAL) was performed. Bacterial culture of BAL was negative while respiratory virus PCR confirmed positivity for HBoV. Antibiotic therapy was discontinued. The patient gradually recovered.

Conclusions: Emerging infectious diseases are a notorious threat for immunocompromised populations such as solid tumor patients. This case is unique because to our knowledge this is the first case report article of HBoV in a solid tumor patient and because imaging techniques exhibited signs of congestive heart failure that did not correlate with the rest of the tests. It shows that unusual pathogens should be considered when managing serious clinical complications with uncommon presentations in cancer patients. Notable diagnostic efforts should be made to reach a diagnosis in these cases.
Case Report: Fortuitous discovery of cor triatriatum sinister in a young adult
Authors: Asma Achour , Ben Slima Mohamed Kacem , Ikram Chamtouri , Ammar Aida , Abdelali Mabrouk , Saad Jamel , Hmida Badii , Zrig Ahmed , Ben Massoud Mejdi , Mnari Walid , Maatouk Mezri
Published: February 2022

Cor triatriatum is an extremely rare cardiac congenital malformation characterized by subdivision of the left atrium into two chambers. This division is due to the presence of an abnormal fibromuscular membrane interrupted by one or more openings that communicate the two chambers. The  size and number of those orifices is variable, affecting the age of onset of symptoms and their severity. Our case describes the fortuitous discovery of this pathology in a young adult in her forties, following the finding of atrial fibrillation during a preoperative assessment of a strangulated hernia. The cardiac ultrasound allowed in our case to invoke the diagnosis, confirmed thereafter with an angioscanner.  Surgical resection was not required in our patient who was put on medical treatment involving a beta-blocker to reduce atrial fibrillation and an anticoagulant treatment to decrease the thromboembolic risk, with a good clinical evolution. It seems therefore interesting to consider this uncommon pathology which may be latent for a long time, manifesting after some physiological or pathological situations.
Current management of adults receiving oral anti-cancer medications: A scoping review protocol
Authors: Richmond Janice P. , Kelly Mary Grace , Johnston Alison , Hynes Lisa , Murphy Patrick J. , Murphy Andrew W.
Published: February 2022

Oncology has been undergoing a profound transition in the last ten years with the increased usage in oral anti-cancer medication. Approximately 25% of all anti-cancer medication is now designed for oral use and this is likely to increase prospectively. These treatments are convenient for patients and are often preferred by them, yet there are similar safety and toxicity concerns as there are to intravenous treatment. Oral anti-cancer medications (OAMs) have the potential to alleviate capacity issues in cancer treating units as patients receive their treatment at home, however there remains a requirement for safe and efficient assessment and care. Consequently, the management of patients on OAMs is of paramount importance. The optimum setting, whether within primary or secondary care, in addition to the appropriate health care professional to carry out patient assessment and monitoring needs to be established.

This paper presents a protocol for a scoping review which aims to systematically and comprehensively map the literature on the current management of adults receiving OAMs. The review will follow the published guidance to direct the various steps involved. The protocol will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework to ensure methodological and reporting quality. Independent full text review will be performed by two reviewers and any disagreements resolved through discussion with a third reviewer. The process will be iterative in nature.

This scoping review will provide a narrative synthesis and map the literature on the management of individuals receiving OAMs. This work is an appropriate initial stage in presenting the literature to inform the subsequent steps in a multi-phased research study which aims to establish and analyse the safety and efficacy of an integrated care model for the management of patients receiving OAM in the community by an advanced practitioner.