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Castrate resistant radiation

Ambreen Khawar, Elisabeth Eppard, Jean Phlippe Sinnes, Frank Roesch, Hojjat Ahmadzadehfar, Stefan Kürpig, Michael Meisenheimer, Florian C Gaertner, Markus Essler, Ralph A Bundschuh
AIM: [Sc]Sc-PSMA-617 with 3.9-hour half-life, in vitro and in vivo characteristics similar to [Lu]Lu-PSMA-617 and possibility of delayed imaging after 24 hours or later, implies it to be advantageous than [ Ga]Ga-PSMA-617 for pretherapeutic dosimetric assessment for [Lu]Lu-PSMA-617 in metastatic castration-resistant prostate carcinoma (mCRPC) patients. In this study, we investigated biodistribution and radiation exposure to normal organs with [Sc]Sc-PSMA-617 in mCRPC patients. METHODS: Five mCRPC patients (mean age, 69 years) enrolled for [Lu]Lu-PSMA-617 therapy were injected with 40-62 MBq [Sc]Sc-PSMA-617 intravenously; Siemens Biograph 2 PET/CT system was used to acquire dynamic PET data (30 minutes) in list mode over the abdomen, followed by the collection of static PET/CT images (skull to mid-thigh) at 45 minutes, 2 and approximately 20 hours postinjection...
February 27, 2018: Clinical Nuclear Medicine
Harman Chopra, Zara Khan, Jamie Contreras, Herui Wang, Abanob Sedrak, Yan Zhu
Castration-resistant prostate cancer (CRPC) frequently develops after initial standard radiation and androgen deprivation therapy, leaving patients with limited further treatment options. Androgen receptor (AR) is a transcription factor that plays a key role in the initiation and progression of prostate cancer. p53, a major tumor suppressor that is rarely mutated in early-stages of prostate cancer, is often deregulated during prostate cancer progression. Here, we report an unusual co-amplification of MDM2 and MDMX, two crucial negative regulators of p53, in CRPC datasets...
January 19, 2018: Oncotarget
Nupam P Mahajan, Domenico Coppola, Jongphil Kim, Harshani R Lawrence, Nicholas J Lawrence, Kiran Mahajan
Prostate cancer stem-like cells (PCSCs) are not only enriched in the CD44+PSA-/lo subpopulation but also employ androgen-independent signaling mechanisms for survival. CD44+ PCSCs defy androgen deprivation, resist chemo- and radiotherapy and are highly tumorigenic. Human prostate tissue microarray (TMA) staining revealed an increased membranous staining of CD44 in the luminal compartment in higher grade G7-G9 tumors versus staining of the basal layer in benign hyperplasia. To uncover tyrosine kinase/s critical for the survival of the CD44+PSA-/lo subpopulation, we performed an unbiased screen targeting 87 tyrosine kinases with gene specific siRNAs...
January 31, 2018: Scientific Reports
Thu-Cuc Nguyen, Ravneet Bajwa, Shahla Bari, Azka Ali, William Paul Skelton, Roland-Austin Federico, Rohit Bishnoi, Justin W Wray, Robert A Zlotecki, Long H Dang, Jameel Muzaffar
Castration-resistant prostate cancer is an incurable disease. To date, six agents-abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T- have shown clinical efficacy in phase III clinical trials, leading to their FDA approval. Patients are typically sequenced through most or all of these agents, and then eventually succumb to their disease. Development of new treatments remains an unmet need. We report a case of a patient who progressed on enzalutamide with a single enlarging metastatic lesion, was treated with ablative stereotactic body radiation therapy while maintaining the same systemic treatment, who then had durable complete remission...
January 2018: Oxford Medical Case Reports
William C Jackson, Krithika Suresh, Vasu Tumati, Steven G Allen, Robert T Dess, Simpa S Salami, Arvin George, Samuel D Kaffenberger, David C Miller, Jason W D Hearn, Shruti Jolly, Rohit Mehra, Brent K Hollenbeck, Ganesh S Palapattu, Matthew Schipper, Felix Y Feng, Todd M Morgan, Neil B Desai, Daniel E Spratt
BACKGROUND: Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design. OBJECTIVE: To identify a potential ICE for men receiving PORT. DESIGN, SETTING, AND PARTICIPANTS: We performed an institutional review board-approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013...
January 3, 2018: European Urology
Miriam Hegemann, Moritz Maas, Steffen Rausch, Simon Walz, Jens Bedke, Arnulf Stenzl, Tilman Todenhöfer
Bone metastases have a major impact on quality of life and survival of patients with advanced prostate cancer. In the last decade, the development and approval of substances inhibiting the vicious cycle of bone metastases have enabled the reduction of complications caused by bone metastases in patients with castration-resistant prostate cancer. These drugs have raised awareness of the importance of skeletal-related events which in the meantime represent an important end point also in trials using agents not specifically designed for bone lesions...
December 29, 2017: Asian Journal of Andrology
Thorsten D Poeppel, Daria Handkiewicz-Junak, Michael Andreeff, Alexander Becherer, Andreas Bockisch, Eva Fricke, Lilli Geworski, Alexander Heinzel, Bernd J Krause, Thomas Krause, Markus Mitterhauser, Wilfried Sonnenschein, Lisa Bodei, Roberto C Delgado-Bolton, Michael Gabriel
Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer...
December 12, 2017: European Journal of Nuclear Medicine and Molecular Imaging
Giulia Riva, Giulia Marvaso, Matteo Augugliaro, Dario Zerini, Cristiana Fodor, Gennaro Musi, Ottavio De Cobelli, Roberto Orecchia, Barbara Alicja Jereczek-Fossa
Objectives: The current standard of care for patients with metastatic prostate cancer (mPCa) at diagnosis is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to define the role of a local radiotherapy (RT) treatment in the mPCa setting. Methods: We retrospectively reviewed data of patients with PCa and bone oligometastases at diagnosis treated in our institution with ADT followed by cytoreductive prostate-RT with or without RT on metastases...
2017: Ecancermedicalscience
Elisabeth Eppard, Ana de la Fuente, Martina Benešová, Ambreen Khawar, Ralph A Bundschuh, Florian C Gärtner, Barbara Kreppel, Klaus Kopka, Markus Essler, Frank Rösch
BACKGROUND: Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications...
2017: Theranostics
Jason Hu, Armen G Aprikian, Fabio L Cury, Marie Vanhuyse, Ahmed S Zakaria, Patrick O Richard, Sylvie Perreault, Alice Dragomir
INTRODUCTION: Late locoregional complications in prostate cancer (PCa) affect quality of life and require medical interventions. Our objective was to compare late locoregional complications in men dying of castration-resistant PCa (CRPC) who previously received external-beam radiotherapy (EBRT) to radical prostatectomy (RP). No group without previous primary local treatment was included. PATIENTS AND METHODS: The cohort consists of CRPC patients who died between 2001 and 2013 and who underwent previous EBRT or RP...
September 5, 2017: Clinical Genitourinary Cancer
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with (177)Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with (223)Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of (177)Lu-PSMA-617 after exposure to more cycles of (223)Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with (223)Ra...
August 15, 2017: Oncotarget
A Dragomir, J Rocha, M Vanhuyse, F L Cury, W Kassouf, J Hu, A G Aprikian
INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases...
August 2017: Current Oncology
C González Ruiz de León, M Ramírez Backhaus, M Sobrón Bustamante, J Casaña, L Arribas, J Rubio-Briones
INTRODUCTION AND OBJECTIVE: There is growing interest in the use of more aggressive therapeutic modalities for treating metastatic prostate cancer. In this study, we examine the use of stereotactic body radiation therapy (SBRT) for patients with oligorecurrent prostate cancer. We analysed the biochemical response and toxicity of patients who underwent this therapy at our centre. MATERIAL AND METHOD: We selected patients who experienced oligorecurrence between January 2015 to December 2016 and were administered SBRT...
December 2017: Actas Urologicas Españolas
R Jeroen A van Moorselaar
Patients with castration-resistant prostate cancer still need a urologist or radiation oncologist for treatment of local complications. Symptomatic progression will be reduced with treatment of the primary tumour.
December 2016: European Urology Focus
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
Levent Kabasakal, Türkay Toklu, Nami Yeyin, Emre Demirci, Mohammad Abuqbeitah, Meltem Ocak, Aslan Aygün, Emre Karayel, Hüseyin Pehlivanoğlu, Nalan Alan Selçuk
OBJECTIVE: The aim of the study was to estimate the radiation-absorbed doses and to study the in vivo and in vitro stability as well as pharmacokinetic characteristics of lutetium-177 (Lu-177) prostate-specific membrane antigen (PSMA)-617. METHODS: For this purpose, 7 patients who underwent Lu-177-PSMA therapy were included into the study. The injected Lu-177-PSMA-617 activity ranged from 3.6 to 7.4 GBq with a mean of 5.2±1.8 GBq. The stability of radiotracer in saline was calculated up to 48 h...
June 1, 2017: Molecular Imaging and Radionuclide Therapy
Vasu Tumati, William C Jackson, Ahmed E Abugharib, Ganesh Raj, Claus Roehrborn, Yair Lotan, Kevin Courtney, Aditya Bagrodia, Jeffrey C Gahan, Zachary S Zumsteg, Michael R Folkert, Aaron M Laine, Raquibul Hannan, Daniel E Spratt, Neil B Desai
OBJECTIVES: To describe the natural history of prostate cancer in men who experience a second biochemical recurrence (BCR) after salvage radiotherapy (SRT) after prostatectomy. PATIENTS AND METHODS: After undergoing SRT at one of two institutions between 1986 and 2013, 286 patients experienced a second BCR, defined as two rises in prostate-specific antigen (PSA) of ≥0.2 ng/mL above nadir. Event rates for distant metastasis (DM) or freedom from DM (FFDM), castration-resistant prostate cancer (CRPC), prostate cancer-specific survival (PCSS), and overall survival (OS) were estimated using the Kaplan-Meier method...
June 5, 2017: BJU International
Timothy L Sita, Katarina G Petras, Q Eileen Wafford, Mark A Berendsen, Tim J Kruser
Intracranial metastasis from prostate cancer is rare. As treatment of castration-resistant prostate cancer improves, the incidence of men with intracranial metastasis from prostate cancer is increasing. Radiation therapy for treatment of intracranial metastasis from prostate cancer is systematically reviewed. A comprehensive review examining peer-reviewed, English language articles from 1990 to 2015 was performed on multiple databases, yielding 1274 articles. These articles were reviewed and selected for studies that met the following inclusion criteria: (1) patients with intracranial metastases from prostate cancer; (2) patients underwent radiation therapy as primary or adjuvant therapy; (3) the sample size of patients was larger than 2...
July 2017: Journal of Neuro-oncology
Esther W Bouman-Wammes, Joyce M van Dodewaard-De Jong, Max Dahele, Matthijs C F Cysouw, Otto S Hoekstra, R Jeroen A van Moorselaar, Maartje A H Piet, Hein J Verberne, Adriaan D Bins, Henk M W Verheul, Ben J Slotman, Daniela E Oprea-Lager, Alfons J M Van den Eertwegh
INTRODUCTION: For patients with oligometastatic recurrence of prostate cancer (PC), stereotactic body radiation therapy (SBRT) represents an attractive treatment option, as it is safe without major side effects. The aim of this study was to investigate the impact of SBRT in delaying the start of androgen deprivation therapy (ADT). PATIENTS AND METHODS: Forty-three patients treated with SBRT for oligometastatic recurrence (< 5 metastases) of hormone-sensitive PC, defined with [(18)F]fluoromethylcholine positron emission tomography/computed tomography were included...
March 29, 2017: Clinical Genitourinary Cancer
Teele Kuusk, Kristiina Pulliainen, Markku H Vaarala
Patients who undergo early androgen-deprivation therapy for prostate cancer may eventually develop castration-resistant prostate cancer. However, no optimal treatment for non-metastasized castration-resistant prostate cancer has yet been established. In the present retrospective, single-institutional study, the radiotherapy (RT) outcomes were evaluated in patients who underwent androgen-deprivation therapy for non-metastatic prostate cancer and subsequently developed castration-resistant disease. Following a thorough chart review, the data of 21 patients with castration-resistant prostate cancer who were treated between 2000 and 2010 with external beam radiation therapy (EBRT) at a prostate radiation dose of >45 Gy were evaluated...
March 2017: Molecular and Clinical Oncology
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