Effectiveness of First-line Immune Checkpoint Blockade Versus Carboplatin-based Chemotherapy for Metastatic Urothelial Cancer

Feld, Emily; Harton, Joanna; Meropol, Neal J.; Adamson, Blythe; Cohen, Aaron B.; Parikh, Ravi B.; Galsky, Matthew D.; Narayan, Vivek; Christodouleas, John P.; Vaughn, David J.; Hubbard, Rebecca A.; Mamtani, Ronac

doi:10.1016/j.eururo.2019.07.032

Cited by 40 publications

(41 citation statements)

References 25 publications

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“…The long-term benefit of first-line immunotherapy compared to carboplatin-based chemotherapy was recently reported in patients with metastatic or locally advanced urothelial carcinoma ( 5 ). In this new era of immuno-oncology, the treatment paradigm is shifting toward restoring tumor elimination by the immune system.…”

Section: Response Evaluationmentioning

confidence: 99%

“…Recent advances in the field of immunotherapy are reshaping the therapeutic landscape for patients with BC. Specifically, immune checkpoints inhibitors (ICIs) have demonstrated promising results in both localized and metastatic settings (4)(5)(6). To date, five anti-PD(L)1 monoclonal antibodies have been approved by the US Food and Drug Administration in the second-line setting.…”

Section: Introductionmentioning

confidence: 99%

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The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

et al. 2020

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Bladder cancer (BC) is the 10th most common cancer worldwide. Approximately one quarter of patients with BC have muscle-invasive disease (MIBC). Muscle-invasive disease carries a poor prognosis and choosing the optimal treatment option is critical to improve patients’ outcomes. Ongoing research supports the role of 2-deoxy-2-(18F)fluoro- D -glucose positron emission tomography (18F-FDG PET) in guiding patient-specific management decisions throughout the course of MIBC. As an imaging modality, 18F-FDG PET is acquired simultaneously with either computed tomography (CT) or MRI to offer a hybrid approach combining anatomical and metabolic information that complement each other. At initial staging, 18F-FDG PET/CT enhances the detection of extravesical disease, particularly in patients classified as oligometastatic by conventional imaging. 18F-FDG PET/CT has value in monitoring response to neoadjuvant and systemic chemotherapy, as well as in localizing relapse after treatment. In the new era of immunotherapy, 18F-FDG PET/CT may also be useful to monitor treatment efficacy as well as to detect immune-related adverse events. With the advent of artificial intelligence techniques such as radiomics and deep learning, these hybrid medical images can be mined for quantitative data, providing incremental value over current standard-of-care clinical and biological data. This approach has the potential to produce a major paradigm shift toward data-driven precision medicine with the ultimate goal of personalized medicine. In this review, we highlight current literature reporting the role of 18F-FDG PET in supporting personalized management decisions for patients with MIBC. Specific topics reviewed include the incremental value of 18F-FDG PET in prognostication, pre-operative planning, response assessment, prediction of recurrence, and diagnosing drug toxicity.

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Section: Response Evaluationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

et al. 2020

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“…More recently, immune checkpoint inhibitors (ICIs) have demonstrated robust evidence of therapeutic activity in metastatic MIBC [ 3 , 5 ]. However, response rates from these uncontrolled immunotherapy trials are less than 30% [ 6 ]. Worse still, a retrospective cohort study shows decreased survival in patients treated with immunotherapy monotherapy relative to the chemotherapy arms [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer

et al. 2021

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Background Cisplatin (CDDP) has become a standard-of-care treatment for muscle-invasive bladder cancer (MIBC), while chemoresistance remains a major challenge. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the regulatory functions as well as complexities of circRNAs in modulating CDDP-based chemotherapy in bladder cancer are yet to be well revealed. Methods Through analyzing the expression profile of circRNAs in bladder cancer tissues, RNA FISH, circRNA pull-down assay, mass spectrometry analysis and RIP, circLIFR was identified and its interaction with MSH2 was confirmed. The effects of circLIFR and MSH2 on CDDP-based chemotherapy were explored by flow cytometry and rescue experiments. Co-IP and Western blot were used to investigate the molecular mechanisms underlying the functions of circLIFR and MSH2. Biological implications of circLIFR and MSH2 in bladder cancer were implemented in tumor xenograft models and PDX models. Results CircLIFR was downregulated in bladder cancer and expression was positively correlated with favorable prognosis. Moreover, circLIFR synergizing with MSH2, which was a mediator of CDDP sensitivity in bladder cancer cells, positively modulated sensitivity to CDDP in vitro and in vivo. Mechanistically, circLIFR augmented the interaction between MutSα and ATM, ultimately contributing to stabilize p73, which triggered to apoptosis. Importantly, MIBC with high expression of circLIFR and MSH2 was more sensitive to CDDP-based chemotherapy in tumor xenograft models and PDX models. Conclusions CircLIFR could interact with MSH2 to positively modulate CDDP-sensitivity through MutSα/ATM-p73 axis in bladder cancer. CircLIFR and MSH2 might be act as promising therapeutic targets for CDDP-resistant bladder cancer.

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“…SEER and NPCR have been well established as research resources since their inception in 1973 and 1992, respectively. As the most recent of the three sources, data derived from Flatiron Health have become a research resource in the last five years (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18); therefore, it has become increasingly critical to understand their features. SEER and NPCR collect specific incident disease data points in a systematic and ordered fashion, fulfilling a public health reporting mandate justified by the public health burden of cancer as a disease.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Population Characteristics in Real-World Clinical Oncology Databases in the US: Flatiron Health, SEER, and NPCR

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Moon

et al. 2020

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Background and Objective The Surveillance, Epidemiology, and End Results Program (SEER) program and the National Program of Cancer Registries (NPCR), are authoritative sources for population cancer surveillance and research in the US. An increasing number of recent oncology studies are based on the electronic health record (EHR)-derived de-identified databases created and maintained by Flatiron Health. This report describes the differences in the originating sources and data development processes, and compares baseline demographic characteristics in the cancer-specific databases from Flatiron Health, SEER, and NPCR, to facilitate interpretation of research findings based on these sources. Methods Patients with documented care from January 1, 2011 through May 31, 2019 in a series of EHR-derived Flatiron Health de-identified databases covering multiple tumor types were included. SEER incidence data (obtained from the SEER 18 database) and NPCR incidence data (obtained from the US Cancer Statistics public use database) for malignant cases diagnosed from January 1, 2011 to December 31, 2016 were included. Comparisons of demographic variables were performed across all disease-specific databases, for all patients and for the subset diagnosed with advanced-stage disease. Results As of May 2019, a total of 201,570 patients with 19 different cancer types were included in Flatiron Health datasets. In an overall comparison to national cancer registries, patients in the Flatiron Health databases had similar sex and geographic distributions, but appeared to be diagnosed with later stages of disease and their age distribution differs from the other datasets. For variables such as stage and race, Flatiron Health databases had a greater degree of incompleteness. There are variations in these trends by cancer types. Conclusions These three databases present general similarities in demographic and geographic distribution, but there are overarching differences across the populations they cover. Differences in data sourcing (medical oncology EHRs vs cancer registries), and disparities in sampling approaches and rules of data acquisition may explain some of these divergences. Furthermore, unlike the steady information flow entered into registries, the availability of medical oncology EHR-derived information reflects the extent of involvement of medical oncology clinics at different points in the specialty management of individual diseases, resulting in inter-disease variability. These differences should be considered when interpreting study results obtained with these databases.

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Effectiveness of First-line Immune Checkpoint Blockade Versus Carboplatin-based Chemotherapy for Metastatic Urothelial Cancer

Cited by 40 publications

References 25 publications

The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer

Comparison of Population Characteristics in Real-World Clinical Oncology Databases in the US: Flatiron Health, SEER, and NPCR

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