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Castrate resistant radiation

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https://www.readbyqxmd.com/read/28220804/impact-of-symptomatic-skeletal-events-on-health-care-resource-utilization-and-quality-of-life-among-patients-with-castration-resistant-prostate-cancer-and-bone-metastases
#1
R McKay, B Haider, M S Duh, A Valderrama, M Nakabayashi, M Fiorillo, L Ristovska, L Wen, P Kantoff
BACKGROUND: Data regarding the impact of symptomatic skeletal events (SSEs) on health economics and patient-reported outcomes in men with castration-resistant prostate cancer (CRPC) and bone metastases from a clinical setting are lacking. Hence, this study aimed to quantify the effects of SSEs on health-care resource utilization (HRU), health-related quality of life (HRQoL) and pain in men with CRPC metastasized to bone. METHODS: This cohort study included men with CRPC and bone metastasis treated at a tertiary center during December 1996-July 2015...
February 21, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28216330/-223-ra-dichloride-spectrometric-characterization-searching-for-the-presence-of-long-lived-isotopes-with-radiological-protection-implications
#2
J Sánchez-Jiménez, A López-Montes, L Núñez-Martínez, A Villa-Abaunza, L M Fraile, V Sánchez-Tembleque, J M Udías
(223)Ra-dichloride was approved with the commercial name of Xofigo in 2014 for treatment of metastatic castration-resistant prostate cancer. (223)Ra is obtained by neutron irradiation of (226)Ra yielding (227)Ac, which decays to (227)Th and (223)Fr, both decaying to (223)Ra. Since (223)Ra is predominantly (95.3%) an alpha emitter with a 11.42days long half-life, the radiopharmaceutical, its remnants, the patient, and waste material can be managed and disposed with low radiation protection requirements. (227)Ac is a long-lived (T1/2=21...
February 16, 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28215159/the-potential-roles-of-radionanomedicine-and-radioexosomic-in-prostate-cancer-research-and-treatment
#3
Martin K Bakht, So Won Oh, Do Won Hwang, Yun-Sang Lee, Hyewon Youn, Lisa A Porter, Gi Jeong Cheon, Cheol Kwak, Dong Soo Lee, Keon Wook Kang
The artificial nanostructures such as nanoparticles and natural nanostructures such as secreted nano-sized extracellular vesicles known as exosomes are promising tools for the realization of personalized medicine. Radionanomedicine is a recently coined term for the simultaneous application of either radiation technology or nuclear medicine with nanomedicine. In addition, radioexosomics is our suggested term for the study of exosomes functions, cytotoxicity, cancerogenicity, and biodistribution using radiation technology and nuclear medicine tracing technology...
February 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28212536/targeting-the-stress-oncoprotein-ledgf-p75-to-sensitize-chemoresistant-prostate-cancer-cells-to-taxanes
#4
Leslimar Ríos-Colón, Christina K Cajigas-Du Ross, Anamika Basu, Catherine Elix, Ivana Alicea-Polanco, Tino W Sanchez, Vinodh Radhakrishnan, Chien-Shing Chen, Carlos A Casiano
Prostate cancer (PCa) is associated with chronic prostate inflammation resulting in activation of stress and pro-survival pathways that contribute to disease progression and chemoresistance. The stress oncoprotein lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, promotes cellular survival against environmental stressors, including oxidative stress, radiation, and cytotoxic drugs. Furthermore, LEDGF/p75 overexpression in PCa and other cancers has been associated with features of tumor aggressiveness, including resistance to cell death and chemotherapy...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185938/folate-targeted-nanoparticle-delivery-of-androgen-receptor-shrna-enhances-the-sensitivity-of-hormone-independent-prostate-cancer-to-radiotherapy
#5
Xinjun Zhang, Nianli Liu, ZhiYing Shao, Hui Qiu, Hong Yao, JiaYin Ji, Jianshe Wang, Wenchao Lu, Ronald C Chen, Longzhen Zhang
Androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa). PCa patients typically receive androgen deprivation therapy; nonetheless, these patients eventually develop castration and radiation resistance. We hypothesized that we could further improve radiotherapeutic efficacy of hormone-independent PCa (HIPC) by silencing AR. In this study, nanoparticle (NP) AR-shRNA was formulated using folate-targeted H1 nanopolymer. We demonstrated that NP AR-shRNA enhances PCa radiosensitivity as indicated by the inhibition of cell growth, increased apoptosis, and increased cell cycle arrest in AR-dependent HIPC in vitro...
February 6, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28103659/-a-case-of-giant-prostate-carcinoma-effectively-treated-with-external-beam-radiation-therapy
#6
Sohei Kanda, Shintaro Narita, Naoki Komine, Seiichi Kitajima, Misa Yamauchi, Akihiro Sugita, Yutaka Saito, Tomonori Habuchi
We present a case of gigantic prostate tumor in a patient with castration-resistant prostate cancer with successful local control by external-beam radiation therapy. A 71-year-old man was shown to have a prostate specific antigen (PSA)level of 24.5 ng/ml, Gleason 9, cT2N1M1a, prostate adenocarcinoma with an estimated prostate volume of 26.9 g. He achieved a PSA nadir at 4 months after the initial androgen deprivation therapy and was diagnosed with castration-resistant prostate cancer three years later. Eight months after the diagnosis of castration-resistant prostate cancer, he visited our hospital due to urinary retention...
December 2016: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28097317/surrogate-end-points-for-all-cause-mortality-in-men-with-localized-unfavorable-risk-prostate-cancer-treated-with-radiation-therapy-vs-radiation-therapy-plus-androgen-deprivation-therapy-a-secondary-analysis-of-a-randomized-clinical-trial
#7
Trevor J Royce, Ming-Hui Chen, Jing Wu, Marian Loffredo, Andrew A Renshaw, Philip W Kantoff, Anthony V D'Amico
Importance: Several surrogates for prostate cancer-specific mortality satisfying the Prentice criteria exist, but whether these are surrogates for all-cause mortality, and how their performance compares, is unknown. Objective: To ascertain and compare the performance of 4 candidate surrogates (prostate-specific antigen [PSA] failure, PSA nadir >0.5 ng/mL, PSA doubling time <9 months, and interval to PSA failure <30 months) for all-cause mortality using the proportion of treatment-effect metric...
January 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28092670/neuropilin-1-is-upregulated-in-the-adaptive-response-of-prostate-tumors-to-androgen-targeted-therapies-and-is-prognostic-of-metastatic-progression-and-patient-mortality
#8
B W C Tse, M Volpert, E Ratther, N Stylianou, M Nouri, K McGowan, M L Lehman, S J McPherson, M Roshan-Moniri, M S Butler, J Caradec, C Y Gregory-Evans, J McGovern, R Das, M Takhar, N Erho, M Alshalafa, E Davicioni, E M Schaeffer, R B Jenkins, A E Ross, R J Karnes, R B Den, L Fazli, P A Gregory, M E Gleave, E D Williams, P S Rennie, R Buttyan, J H Gunter, L A Selth, P J Russell, C C Nelson, B G Hollier
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC)...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28045115/skeletal-related-events-significantly-impact-health-related-quality-of-life-in-metastatic-castration-resistant-prostate-cancer-data-from-prevail-and-affirm-trials
#9
F Saad, C Ivanescu, D Phung, Y Loriot, S Abhyankar, T M Beer, B Tombal, S Holmstrom
BACKGROUND: We investigated the impact of skeletal-related events (SREs) on health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) in phase III trials of enzalutamide versus placebo. METHODS: Patients with mCRPC experiencing at least one SRE during AFFIRM and PREVAIL were assessed for trajectory-adjusted mean change in HRQoL by first SRE using Functional Assessment of Cancer Therapy-Prostate (FACT-P; AFFIRM, three domains, and PREVAIL, nine domains) and EQ-5D (PREVAIL) instruments...
January 3, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/27997745/impact-of-treatment-on-progression-to-castration-resistance-metastases-and-death-in-men-with-localized-high-grade-prostate-cancer
#10
Eric T Miller, Karim Chamie, Lorna Kwan, Michael S Lewis, Beatrice S Knudsen, Isla P Garraway
Men with high-grade prostate cancer (HGPC) are at greatest risk of disease progression. Clinical risk factors associated with castration-resistant prostate cancer (CRPC), metastases, and prostate cancer-specific mortality (PCSM) were identified in a contemporary HGPC cohort. Clinical data was collected from men diagnosed with Gleason sum (GS) ≥8 at the Greater Los Angeles Veterans Affairs (GLA-VA) Healthcare System between 2000 and 2013. Multivariable competing risks regression analyses assessed progression to CRPC, metastases, and PCSM within three treatment strata...
January 2017: Cancer Medicine
https://www.readbyqxmd.com/read/27919966/multimodal-primary-treatment-of-metastatic-prostate-cancer-with-androgen-deprivation-and-radiation
#11
Timo Joensuu, Greetta Joensuu, Kalevi Kairemo, Timo Kiljunen, Maigo Riener, Aili Aaltonen, Martti Ala-Opas, Aki Kangasmäki, Tuomo Alanko, Lauri Taipale, Petteri Hervonen, Anna Bützow, Irene Virgolini, Akseli Hemminki
AIM: We combined anti-androgen therapy with radiotherapy in a first-line setting for metastatic prostate cancer aiming to cause maximal cancer-cell death to delay the emergence of castration-resistant disease. MATERIALS AND METHODS: In this non-randomized retrospective series of 46 patients, the initial median prostate-specific antigen (PSA) was 98.5 μg/l (range=6.7-15,500), median Gleason score 9 and most men had at least T3N1M1 disease. All patients received luteinizing hormone releasing hormone analog or degarelix with bicalutamide...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27896639/seom-clinical-guideline-for-bone-metastases-from-solid-tumours-2016
#12
C Grávalos, C Rodríguez, A Sabino, M Á Seguí, J A Virizuela, A Carmona, J Cassinello, D Isla, C Jara, M Martín
Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease...
December 2016: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#13
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885457/-psma-targeted-radioligand-therapy-in-prostate-cancer
#14
M M Heck, M Retz, R Tauber, K Knorr, C Kratochwil, M Eiber
Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany...
January 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27836248/a-review-for-clinicians-prostate-cancer-and-the-antineoplastic-properties-of-metformin
#15
REVIEW
Stephen J Hankinson, Mina Fam, Nitin N Patel
OBJECTIVES: Metformin has numerous antineoplastic effects including an AMP-activated protein kinase-dependent mechanism, AMP-activated protein kinase-independent mechanisms, alteration of insulin and insulin-like growth factor signaling pathways, and suppression of androgen signaling pathways that trigger prostate cancer growth and proliferation. In contrast to other malignancies that are associated with increased incidence among patients with obesity and type II diabetes mellitus (T2DM), epidemiological studies suggest that obesity and T2DM may impart a protective effect on prostate cancer incidence by creating a set of metabolic conditions that lower androgen levels...
January 2017: Urologic Oncology
https://www.readbyqxmd.com/read/27782913/post-therapeutic-dosimetry-of-177lu-dkfz-psma-617-in-the-treatment-of-patients-with-metastatic-castration-resistant-prostate-cancer
#16
Madhav P Yadav, Sanjana Ballal, Madhavi Tripathi, Nishikant A Damle, Ranjit K Sahoo, Amlesh Seth, Chandrasekhar Bal
OBJECTIVE: Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients...
January 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/27766278/a-metastatic-castration-resistant-prostate-cancer-patient-with-multiple-bone-metastases-has-durable-biochemical-and-radiological-response-to-docetaxel-chemotherapy
#17
Tatsuaki Daimon, Takeo Kosaka, Mototsugu Oya
Docetaxel chemotherapy for metastatic castration resistant prostate cancer patients has been thought palliative because the radiological response rate is low and durable response is rare. The patient was a 64-year-old man who was diagnosed with cT3aN0M0 prostate cancer and underwent external beam radiation therapy as the initial treatment. He underwent androgen deprivation therapy and 8 cycles of docetaxel chemotherapy. His PSA level decreased and became undetectable and the disease was confirmed to be stable by radiological examination...
2016: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/27749328/isotope-therapy-for-castrate-resistant-prostate-cancer-unique-sequencing-and-combinations
#18
Oliver Sartor
Radiopharmaceuticals used in the treatment of castrate-resistant prostate cancer are reviewed herein with an emphasis on sequential and combination therapies. Four bone-seeking radiopharmaceuticals had been approved in the United States. Three of these are β-emitters (phosphorus-32, strontium-89, samarium-153-ethylenediaminetetramethylene-phosphonic acid) that are approved for palliative purposes. One α-emitter (radium-223 [Ra]) is approved for prolongation of survival in bone metastatic castrate-resistant prostate cancer...
September 2016: Cancer Journal
https://www.readbyqxmd.com/read/27749327/immune-therapy-for-prostate-cancer
#19
Oladapo Yeku, Susan F Slovin
Immunotherapy for castration-resistant prostate cancer has continued to be an area of active research over the last several years. The enthusiasm of this approach has been based on the assumption of better tolerability and that using the body's own immune system may be more effective than either hormonal or chemotherapy. Sipuleucel-T, a dendritic cell-based vaccine, is the only approved agent in this class for the management of castrate-resistant prostate cancer. Although sipuleucel-T increases overall survival without any significant changes in progression-free survival, other forms of immunotherapy such as PSA-TRICOM, ipilimumab, and chimeric antigen receptor T cell therapy are in advanced stages of clinical development...
September 2016: Cancer Journal
https://www.readbyqxmd.com/read/27741508/androgen-receptor-dependent-and-independent-mechanisms-driving-prostate-cancer-progression-opportunities-for-therapeutic-targeting-from-multiple-angles
#20
REVIEW
David T Hoang, Kenneth A Iczkowski, Deepak Kilari, William See, Marja T Nevalainen
Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways...
January 10, 2017: Oncotarget
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