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  1. Article ; Online: Immunotherapy and Metastatic Renal Cell Carcinoma

    Nikhita Kathuria-Prakash / Claire Drolen / Christopher A. Hannigan / Alexandra Drakaki

    Life, Vol 12, Iss 24, p

    A Review of New Treatment Approaches

    2022  Volume 24

    Abstract: Introduction: Renal cell carcinomas (RCC) have been treated with immunotherapy for decades; the use of immune checkpoint inhibitors represents the most recent advance. In this review, we compare these new RCC immunotherapies, with a focus on achieving ... ...

    Abstract Introduction: Renal cell carcinomas (RCC) have been treated with immunotherapy for decades; the use of immune checkpoint inhibitors represents the most recent advance. In this review, we compare these new RCC immunotherapies, with a focus on achieving durable complete responses (CR). Review: Sorafenib and sunitinib were the first Food and Drug Administration (FDA)-approved targeted agents for RCC, with sunitinib eventually becoming the standard-of-care agent against which novel therapies are compared. In the last five years, many combination therapies based on the use of immune checkpoint inhibitors (ICIs) and receptor tyrosine kinase inhibitors (TKIs), including ipilimumab/nivolumab, nivolumab/cabozantinib, avelumab/axitinib, pembrolizumab/axitinib, and pembrolizumab/lenvatinib, have demonstrated superior overall survival (OS) and progression-free survival (PFS) compared to sunitinib. Ongoing clinical trials of hypoxia-induced factor-2 alpha (HIF-2a) inhibitors, chimeric antigen receptor T cell (CAR-T) therapy targeting CD70, and other new combination therapies have also shown promise and are currently under investigation. Conclusions: Many new combination therapies are approved for RCC treatment, and CR rates suggest that, in the era of immunotherapy, it may be possible to achieve durable responses and survival benefit in patients with metastatic RCC.
    Keywords renal cell carcinoma ; immunotherapy ; immune checkpoint inhibitors ; sunitinib ; complete response rate ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Treatment Equity in the Immunotherapy Era

    Gavin Hui / Claire Drolen / Christopher A. Hannigan / Alexandra Drakaki

    Life, Vol 12, Iss 360, p

    Options for Patients with Both Autoimmune Disease and GU Cancers

    2022  Volume 360

    Abstract: Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune- ... ...

    Abstract Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune-related adverse events (irAEs). The scope of irAEs is broad, and this paper aims to review the rheumatologic side effects associated with immunotherapy drugs approved for bladder cancer and renal cell carcinoma. IrAEs are graded by the common terminology criteria for adverse events (CTCAE), which ranges from 1 to 5. The management of irAEs includes corticosteroids or other immunosuppressive therapies, and it may require discontinuation of immunotherapy. Several real world experience studies suggest that most patients with pre-existing autoimmune diseases treated with ICI did not have to discontinue treatment due to immune-mediated side effects. While data suggest autoimmune side effects are manageable, patients with pre-existing autoimmune diseases are often excluded from immunotherapy clinical trials. Better understanding of these irAEs will improve its safety and expand its use in those with underlying autoimmune disease.
    Keywords immune checkpoint inhibitors ; autoimmune disease ; renal cancer ; bladder cancer ; immune-related adverse event ; immunotherapy ; Science ; Q
    Subject code 610 ; 616
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Rapidly progressive neurologic decline and morbilliform rash presenting in a patient with lymphoma

    Dean Ehrlich / Jennifer Phan / Gavin Hui / Alexandra Drakaki

    Clinics and Practice, Vol 8, Iss

    2018  Volume 4

    Abstract: A 67-year-old male with past medical history of mantle cell lymphoma and atrial fibrillation presented with a truncal rash, bilateral lower extremity weakness, and confusion. Within three days of presentation, his condition rapidly deteriorated with the ... ...

    Abstract A 67-year-old male with past medical history of mantle cell lymphoma and atrial fibrillation presented with a truncal rash, bilateral lower extremity weakness, and confusion. Within three days of presentation, his condition rapidly deteriorated with the onset of diffuse flaccid paralysis, aphasia, and severe alteration in mental status. Initial results from serum studies, lumbar puncture, magnetic resonance imaging, and electroencephalogram were not diagnostic. However, on the ninth day after initial presentation, the West Nile Virus (WNV) immunoglobulin M antibody returned positive from the cerebrospinal fluid. West Nile Virus encephalitis is endemic worldwide, and is the most common viral encephalitis in the United States. WNV presents in a variety of ways, and the recognition by physicians is crucial due to the estimated 2- 12% mortality rate and significant longterm morbidity of neuroinvasive disease. The initial management and long term prognosis are points of ongoing research. This case represents a particularly profound example of neuroinvasive WNV. Our patient made a significant recovery after his initial presentation with aggressive supportive care, however still suffers from bilateral lower extremity weakness more than a year later.
    Keywords Lymphoma ; Neurologic decline ; Morbilliform rash ; Medicine (General) ; R5-920
    Language English
    Publishing date 2018-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Effects of novel androgen receptor signaling inhibitors on PSMA PET signal intensity in patients with castrate-resistant prostate cancer

    Ida Sonni / Andrei Gafita / Lena M. Unterrainer / Rejah M. Alano / Stephanie Lira / John Shen / Alexandra Drakaki / Tristan Grogan / Matthew B. Rettig / Johannes Czernin / Jeremie Calais

    EJNMMI Research, Vol 13, Iss 1, Pp 1-

    a prospective exploratory serial imaging study

    2023  Volume 8

    Abstract: Abstract Background PSMA expression is influenced by hormonal status. We evaluated changes in PSA and whole-body 68Ga-PSMA-11 PET/CT (WB-PSMA PET) after initiation of androgen receptor signaling inhibitors (ARSi). Methods Prospectively enrolled patients ... ...

    Abstract Abstract Background PSMA expression is influenced by hormonal status. We evaluated changes in PSA and whole-body 68Ga-PSMA-11 PET/CT (WB-PSMA PET) after initiation of androgen receptor signaling inhibitors (ARSi). Methods Prospectively enrolled patients with metastatic castration-resistant prostate cancer (mCRPC) initiating ARSi underwent serial PSA measurements and WB-PSMA PET at baseline, 1-week, and 3-months post-ARSi. We correlated WB-PSMA PET metrics and PSA kinetics after ARSi to 1-year clinical outcome. Results Due to low enrollment rate, the study was closed before reaching the recruitment goal of 30 patients. Nine patients were enrolled. At 1-year, unfavorable outcome was documented in 6/9 (66%) patients. Nine/9 patients completed PSMA PET at 1-week, 5/9 at 3-months. Changes in PSA, PSMA-VOL, SUVmean and SUVmax were − 12%, + 5%, + 3%, and + 10% at 1-week, − 42%, − 16%, − 15% and − 17% at 3-months, respectively. Conclusions Our prospective trial involving 9 mCRPC patients initiating ARSi did not show significant modulation of PSMA expression measured on WB-PSMA PET at 1-week. This study was registered on clinicaltrials.gov (NCT04279561).
    Keywords PSMA PET ; Hormonal treatment ; Androgen receptor ; Prostate cancer ; PSMA flare ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Associations of quantitative whole-body PSMA-PET metrics with PSA progression status under long-term androgen deprivation therapy in prostate cancer patients

    Vishnu Murthy / Emmanuel Appiah-Kubi / Kathleen Nguyen / Pan Thin / Masatoshi Hotta / John Shen / Alexandra Drakaki / Matthew Rettig / Andrei Gafita / Jeremie Calais / Ida Sonni

    European Journal of Hybrid Imaging, Vol 7, Iss 1, Pp 1-

    a retrospective single-center study

    2023  Volume 13

    Abstract: Abstract Purpose To evaluate whether quantitative whole-body (WB) PSMA-PET metrics under long-term androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors (ARSi) are associated with PSA progression. Methods Patients who underwent ...

    Abstract Abstract Purpose To evaluate whether quantitative whole-body (WB) PSMA-PET metrics under long-term androgen deprivation therapy (ADT) and/or androgen receptor signaling inhibitors (ARSi) are associated with PSA progression. Methods Patients who underwent at least 2 68Ga-PSMA-11 PET/CT scans between October 2016 and April 2021 (n = 372) and started a new line of ADT ± ARSi between PET1 and PET2 were retrospectively screened for inclusion. We investigated the association between PCWG3-defined PSA progression status at PET2 and the following PSMA-PET parameters: appearance of new lesions on PET2, ≥ 20% increase in WB-PSMA tumor volume (WB-PSMA-VOL), progression of disease (PD) by RECIP 1.0, and ≥ 30% increase in WB-PSMA-SUVmean from PET1 to PET2. Spearman’s rank correlation coefficients and Fisher’s exact test were used to evaluate the associations. Results Thirty-five patients were included: 12/35 (34%) were treated with ADT only and 23/35 (66%) with ARSi ± ADT. The median time between PET1 and PET2 was 539 days. Changes (%) in median PSA levels, WB-PSMA-SUVmean, and WB-PSMA-VOL from PET1 to PET2 were -86%, -23%, and -86%, respectively. WB-PSMA-VOL ≥ 20%, new lesions, RECIP-PD, and WB-PSMA-SUVmean ≥ 30% were observed in 5/35 (14%), 9/35 (26%), 5/35 (14%), and 4/35 (11%) of the whole cohort, in 3/9 (33%), 7/9 (78%), 3/9 (33%), and 2/9 (22%) of patients with PSA progression at PET2, and in 2/26 (8%), 2/26 (8%), 2/26 (8%), and 2/26 (8%) of patients without PSA progression at PET2 (p = 0.058, p < 0.001, p = 0.058, p = 0.238, respectively). Changes in PSA were correlated to percent changes in WB-PSMA-VOL and WB-PSMA-SUVmean (Spearman ρ: 0.765 and 0.633, respectively; p < 0.001). Conclusion Changes in PSA correlated with changes observed on PSMA-PET, although discordance between PSA and PSMA-PET changes was observed. Further research is necessary to evaluate if PSMA-PET parameters can predict progression-free survival and overall survival and serve as novel endpoints in clinical trials.
    Keywords PSMA-PET ; ADT ; ARSi ; RECIP ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
    Subject code 610
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: MicroRNA-gene signaling pathways in pancreatic cancer

    Alexandra Drakaki / Dimitrios Iliopoulos

    Biomedical Journal, Vol 36, Iss 5, Pp 200-

    2013  Volume 208

    Abstract: Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial ... ...

    Abstract Pancreatic cancer is the fourth most frequent cause of cancer-related deaths and is characterized by early metastasis and pronounced resistance to chemotherapy and radiation therapy. Despite extensive esearch efforts, there is not any substantial progress regarding the identification of novel drugs against pancreatic cancer. Although the introduction of the chemotherapeutic agent gemcitabine improved clinical response, the prognosis of these patients remained extremely poor with a 5-year survival rate of 3-5%. Thus, the identification of the novel molecular pathways involved in pancreatic oncogenesis and the development of new and potent therapeutic options are highly desirable. Here, we describe how microRNAs control signaling pathways that are frequently deregulated during pancreatic oncogenesis. In addition, we provide evidence that microRNAs could be potentially used as novel pancreatic cancer therapeutics through reversal of chemotherapy and radiotherapy resistance or regulation of essential molecular pathways. Further studies should integrate the deregulated genes and microRNAs into molecular networks in order to identify the central regulators of pancreatic oncogenesis. Targeting these central regulators could lead to the development of novel targeted therapeutic approaches for pancreatic cancer patients.
    Keywords genes ; microRNAs ; networks ; pancreatic cancer ; systems biology ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2013-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Outcomes with multi-disciplinary management of central lung tumors with CT-guided percutaneous high dose rate brachyablation

    Stephanie M. Yoon / Robert Suh / Fereidoun Abtin / Drew Moghanaki / Scott Genshaft / Mitchell Kamrava / Alexandra Drakaki / Sandy Liu / Puja Venkat / Alan Lee / Albert J. Chang

    Radiation Oncology, Vol 16, Iss 1, Pp 1-

    2021  Volume 9

    Abstract: Abstract Background Centrally located lung tumors present treatment challenges given their proximity to mediastinal structures including the central airway, esophagus, major vessels, and heart. Therapeutic options can be limited for medically inoperable ... ...

    Abstract Abstract Background Centrally located lung tumors present treatment challenges given their proximity to mediastinal structures including the central airway, esophagus, major vessels, and heart. Therapeutic options can be limited for medically inoperable patients, particularly if they have received previous thoracic radiotherapy. High dose rate (HDR) brachyablation was developed to improve the therapeutic ratio for patients with central lung tumors. The purpose of this study is to report initial safety and efficacy outcomes with this treatment for central lung malignancies. Methods From September 2015 to August 2019, a total of 25 patients with 37 pulmonary tumors were treated with percutaneous HDR brachyablation. Treatment was delivered by a multi-disciplinary team of interventional radiologists, pulmonologists, and radiation oncologists. Twenty-three patients received a median dose of 21.5 Gy (range 15–27.5) in a single fraction, whereas two patients received median dose of 24.75 Gy (range 24–25.5) over 2–3 fractions. Tumor local control (LC) was evaluated by Response Evaluation Criteria in Solid Tumors v1.1. Treatment-related toxicities were graded by Common Terminology Criteria for Adverse Events v5.0, with adverse events less than 90 days defined as acute, and those occurring later were defined as late. LC, progression-free survival (PFS), and overall survival (OS) rates were estimated by the Kaplan–Meier method. Results Of 37 treated tumors, 88% were metastatic. Tumor location was central and ultra-central in 24.3% and 54.1%, respectively. Average tumor volume was 11.6 cm3 (SD 12.4, range 0.57–62.8). Median follow-up was 19 months (range 3–48). Two–year LC, PFS, and OS were 96.2%, 29.7%, and 65.5%, respectively. Thirteen of 39 (33.3%) catheter implantation procedures were associated with trace minor pneumothorax requiring no intervention, 1 (2.5%) procedure with minor radiographic pulmonary hemorrhage, and 4 (10.3%) with major pneumothorax requiring chest tube insertions. All procedural complications ...
    Keywords Brachytherapy ; Interstitial brachytherapy ; High-dose-rate brachytherapy ; Brachyablation ; Pulmonary metastasis ; Medical physics. Medical radiology. Nuclear medicine ; R895-920 ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
    Subject code 616 ; 610
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial

    Michiel S. van der Heijden / Thomas Powles / Daniel Petrylak / Ronald de Wit / Andrea Necchi / Cora N. Sternberg / Nobuaki Matsubara / Hiroyuki Nishiyama / Daniel Castellano / Syed A. Hussain / Aristotelis Bamias / Georgios Gakis / Jae-Lyun Lee / Scott T. Tagawa / Ulka Vaishampayan / Jeanny B. Aragon-Ching / Bernie J. Eigl / Rebecca R. Hozak / Erik R. Rasmussen /
    Meng Summer Xia / Ryan Rhodes / Sameera Wijayawardana / Katherine M. Bell-McGuinn / Amit Aggarwal / Alexandra Drakaki

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 15

    Abstract: Identification of biomarkers to stratify patients who might benefit from treatment is needed to optimize targeted therapies. Here, based on an analysis of the RANGE trial (NCT02426125), the authors report potentially predictive biomarkers for survival ... ...

    Abstract Identification of biomarkers to stratify patients who might benefit from treatment is needed to optimize targeted therapies. Here, based on an analysis of the RANGE trial (NCT02426125), the authors report potentially predictive biomarkers for survival benefit in patients with platinum-refractory advanced urothelial carcinoma treated with the anti-VEGFR2 monoclonal antibody ramucirumab.
    Keywords Science ; Q
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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